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US 2023/0357852 A1Published application
Detecting non-hodgkin lymphoma
AssigneesMayo Foundation for Medical Education and Research, Exact Sciences Development Company, LLC
InventorsJohn B. Kisiel, Douglas W. Mahoney, David A. Ahlquist, William R. Taylor, Hatim T. Allawi, Viatcheslav E. Katerov
Life of this patent
Estimating the term…
Abstract
Provided herein is technology for cancer screening and particularly, but not exclusively, to methods, compositions, and related uses for detecting the presence of non-Hodgkin lymphoma (NHL) and NHL subtypes (e.g., diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, peripheral T-cell lymphoma).
Claims148
A method for characterizing a biological sample comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from:
- (i) ADRA1D, DNAH14_A, FAM110B, FAM221A, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644047-184644181, MAX.chr5:74349626-74349841, MAX.chr5:74349626-74349841, MAX.chr6.19805123-19805338, MNX1, NRN1_A, SH3BP4, SYT6, VWA5B1, and ZNF503;
- (ii) BNC1_B, ADRAID, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B;
- (iii) BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FOXP4, ITGA5, JUP, MAX.chr1.61508719-61508998, MAX.chr3.44038141-44038266, TGFB1I1, THBS1, and TPBG_C;
- and
- (iv) BNC1_B, ADRAID, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B in a biological sample of a human individual through treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR;
- (b) comparing the methylation level to a methylation level of a corresponding set of genes in control samples without lymphoma;
- and
- (c) determining that the individual has non-Hodgkin lymphoma when the methylation level measured in the one or more genes is higher than the methylation level measured in the respective control samples.
9 more elements
A method for characterizing a biological sample comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) ADRAID, CACNG_B, CDK20 _A, DNAH14_A, EBF3_B, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, and SYT6;
- (ii) ADRAID, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, and TPBG_C;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAM110B, FLRT2, HOXA9, ITGA5, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, TPBG_C, VWASB1, and ZNF503;
- (iv) ADRAID, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, FOXP4, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, and TPBG_C;
- and
- (v) HOXA9, CDK20_B, BNC1_B, DNAH14_B, NRN1_B, SYT2, and CALN1;
- in a biological sample of a human individual through treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR;
- (b) comparing the methylation level to a methylation level of a corresponding set of genes in control samples without lymphoma;
- and
- (c) determining that the individual has follicular lymphoma when the methylation level measured in the one or more genes is higher than the methylation level measured in the respective control samples.
11 more elements
A method for characterizing a biological sample comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) ADRAID, BNC1_B, CACNG8_B, CDK20 _A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, THBS1, TPBG_C, and ZNF503;
- (ii) ADRAID, BNC1_B, CACNG8_B, EBF3_B, FAM110B, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TPBG_C, and ZNF503;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAM110B, FLRT2, FOXP4, GABRG3, GATA6, HOXA9, ITGA5, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503;
- (iv) ADRAID, BNC1_B, CACNG8_B, CDK20 _A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503;
- in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR;
- (b) comparing the methylation level to a methylation level of a corresponding set of genes in control samples without lymphoma;
- and
- (c) determining that the individual has DLBCL cancer when the methylation level measured in the one or more genes is higher than the methylation level measured in the respective control samples.
10 more elements
A method for characterizing a biological sample comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) CACNG8_B, FAM110B, MAX.chr1:61508832-61508969, MAX.chr4.184644069-184644158, and TPBG_C;
- (ii) BNC1_B, FAM110B, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, and MNX1;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, FAM110B, GABRG3, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr6.19805195-19805266, MNX1, NRN1_A, SYT6, TPBG_C, and ZNF503;
- and
- (iv) ADRAID, BNC1_B, CACNG8_B, FAM110B, FOXP4, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MNX1, NRN1_A, and TPBG_C
- in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR;
- (b) comparing the methylation level to a methylation level of a corresponding set of genes in control samples without lymphoma;
- and
- (c) determining that the individual has mantle cell lymphoma when the methylation level measured in the one or more genes is higher than the methylation level measured in the respective control samples.
11 more elements
A method for characterizing a biological sample comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) CACNG8_B, FAM110B, GABRG3, and ITGA5;
- (ii) ADRAID, BNC1_B, GABRG3, HOXA9, ITGA5, and THBS1;
- (iii) BNC1_B, CACNG8_B, FAM110B, GABRG3, HOXA9, ITGA5, and MAX.chr6.19805195-19805266;
- (iv) ADRAID, BNC1_B, CACNG8_B, CDK20_A, FOXP4, GABRG3, HOXA9, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, and THBS1;
- and
- (v) CACNG8_B, ADRAID, TGFB1I1, FAM110B_A, GABRG3, VWA5B1, and ITGA5 in a lymph gland sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR;
- (b) comparing the methylation level to a methylation level of a corresponding set of genes in control samples without lymphoma;
- and
- (c) determining that the individual has marginal zone lymphoma when the methylation level measured in the one or more genes is higher than the methylation level measured in the respective control samples.
11 more elements
A method for characterizing a biological sample comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) CACNG8_B, FOXP4, GABRG3, ITGA5, TGFB1I1, and VWASB1;
- (ii) GABRG3, ITGA5, and JUP;
- (iii) ADRAID, BNC1_B, CACNG8_B, FLRT2, FOXP4, GABRG3, HOXA9, ITGA5, JUP, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, SH3BP4, SYT6, TGFB1I1, and VWASB1;
- (iv) BNC1_B, FOXP4, ITGA5, SH3BP4, SYT6, and TGFB1I1;
- and
- (v) CACNG8_B, ADRAID, TGFB1I1, FAM110B_A, GABRG3, VWA5B1, and ITGA5 in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR;
- (b) comparing the methylation level to a methylation level of a corresponding set of genes in control samples without lymphoma;
- and
- (c) determining that the individual has peripheral T-cell lymphoma when the methylation level measured in the one or more genes is higher than the methylation level measured in the respective control samples.
11 more elements
A method, comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) ADRA1D, DNAH14_A, FAM110B, FAM221A, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644047-184644181, MAX.chr5:74349626-74349841, MAX.chr5:74349626-74349841, MAX.chr6.19805123-19805338, MNX1, NRN1_A, SH3BP4, SYT6, VWA5B1, and ZNF503;
- (ii) BNC1_B, ADRAID, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B;
- (iii) BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FOXP4, ITGA5, JUP, MAX.chr1.61508719-61508998, MAX.chr3.44038141-44038266, TGFB1I1, THBS1, and TPBG_C;
- and
- (iv) BNC1_B, ADRAID, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
7 more elements
A method, comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) ADRAID, CACNG_B, CDK20_A, DNAH14_A, EBF3_B, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, and SYT6;
- (ii) ADRAID, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, and TPBG_C;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAM110B, FLRT2, HOXA9, ITGA5, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, TPBG_C, VWASB1, and ZNF503;
- (iv) ADRAID, BNCI1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, FOXP4, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, and TPBG_C;
- and
- (v) HOXA9, CDK20_B, BNC1_B, DNAH14_B, NRN1_B, SYT2, and CALN1;
- in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
9 more elements
A method, comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) ADRAID, BNC1_B, CACNG8_B, CDK20 _A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, THBS1, TPBG_C, and ZNF503;
- (ii) ADRAID, BNC1_B, CACNG8_B, EBF3_B, FAM110B, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TPBG_C, and ZNF503
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAM110B, FLRT2, FOXP4, GABRG3, GATA6, HOXA9, ITGA5, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503;
- (iv) ADRAID, BNC1_B, CACNG8_B, CDK20 _A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503;
- and
- (v) MAX.chr5:74349626-74349841, HOXA9, BNC1_B, NRN1_B, TPBG_D, SYT2, and CALN1;
- in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
9 more elements
A method, comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) CACNG8_B, FAM110B, MAX.chr1:61508832-61508969, MAX.chr4.184644069-184644158, and TPBG_C;
- (ii) BNC1_B, FAM110B, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-18464415 8, and MNX1;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, FAM110B, GABRG3, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr6.19805195-19805266, MNX1, NRN1_A, SYT6, TPBG_C, and ZNF503;
- and
- (iv) ADRAID, BNC1_B, CACNG8_B, FAM110B, FOXP4, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MNX1, NRN1_A, and TPBG_C
- in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
8 more elements
A method, comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) CACNG8_B, FAM110B, GABRG3, and ITGA5;
- (ii) ADRAID, BNC1_B, GABRG3, HOXA9, ITGA5, and THBS1;
- (iii) BNC1_B, CACNG8_B, FAM110B, GABRG3, HOXA9, ITGA5, MAX.chr6.19805195-19805266;
- (iv) ADRAID, BNC1_B, CACNG8_B, CDK20_A, FOXP4, GABRG3, HOXA9, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, and THBS1;
- and
- (v) CACNG8_B, ADRAID, TGFB1I1, FAM110B_A, GABRG3, VWA5B1, and ITGA5
- in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
9 more elements
A method, comprising:
- (a) measuring a methylation level of a CpG site for one or more genes selected from
- (i) CACNG8_B, FOXP4, GABRG3, ITGA5, TGFB1I1, and VWASB1;
- (ii) GABRG3, ITGA5, and JUP;
- (iii) ADRAID, BNC1_B, CACNG8_B, FLRT2, FOXP4, GABRG3, HOXA9, ITGA5, JUP, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, SH3BP4, SYT6, TGFB1I1, and VWASB1;
- (iv) BNC1_B, FOXP4, ITGA5, SH3BP4, SYT6, and TGFB1I1;
- and
- (v) CACNG8_B, ADRAID, TGFB1I1, FAM110B_A, GABRG3, VWA5B1, and ITGA5 in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the CpG site by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
8 more elements
A method of screening for lymphoma in a sample obtained from a subject, the method comprising:
- 1) assaying a methylation state of a DNA methylation marker comprising a chromosomal region having an annotation selected from the group consisting of one of the following groups:
- (i) ADRA1D, DNAH14_A, FAM110B, FAM221A, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644047-184644181, MAX.chr5:74349626-74349841, MAX.chr5:74349626-74349841, MAX.chr6.19805123-19805338, MNX1, NRN1_A, SH3BP4, SYT6, VWA5B1, and ZNF503;
- (ii) BNC1_B, ADRAID, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B;
- (iii) BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FOXP4, ITGA5, JUP, MAX.chr1.61508719-61508998, MAX.chr3.44038141-44038266, TGFB1I1, THBS1, and TPBG_C;
- and
- (iv) BNC1_B, ADRAID, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B, and
- 2) identifying the subject as having lymphoma when the methylation state of the marker is different than a methylation state of the marker assayed in a subject that does not have lymphoma.
4 more elements
A method of screening for follicular lymphoma in a sample obtained from a subject, the method comprising:
- 1) assaying a methylation state of a DNA methylation marker comprising a chromosomal region having an annotation selected from the group consisting of one of the following groups:
- (i) ADRAID, CACNG_B, CDK20_A, DNAH14_A, EBF3_B, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, and SYT6;
- (ii) ADRAID, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, NRN1 _A, SH3BP4, SYT6, and TPBG_C;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAM110B, FLRT2, HOXA9, ITGA5, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, TPBG_C, VWASB1, and ZNF503;
- (iv) ADRAID, BNCI1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, FOXP4, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, and TPBG_C;
- and
- (v) HOXA9, CDK20_B, BNC1_B, DNAH14_B, NRN1_B, SYT2, and CALN1;
- 2) identifying the subject as having follicular lymphoma when the methylation state of the marker is different than a methylation state of the marker assayed in a subject that does not have lymphoma.
5 more elements
A method of screening for DLBCL in a sample obtained from a subject, the method comprising:
- 1) assaying a methylation state of a DNA methylation marker comprising a chromosomal region having an annotation selected from the group consisting of one of the following groups:
- (i) ADRAID, BNC1_B, CACNG8_B, CDK20 _A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, THBS1, TPBG_C, and ZNF503;
- (ii) ADRAID, BNC1_B, CACNG8_B, EBF3_B, FAM110B, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TPBG_C, and ZNF503;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAM110B, FLRT2, FOXP4, GABRG3, GATA6, HOXA9, ITGA5, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503;
- (iv) ADRAID, BNC1_B, CACNG8_B, CDK20 _A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503, and
- (v) MAX.chr5:74349626-74349841, HOXA9, BNC1_B, NRN1_B, TPBG_D, SYT2, and CALN1;
- 2) identifying the subject as having DLBCL when the methylation state of the marker is different than a methylation state of the marker assayed in a subject that does not have lymphoma.
4 more elements
A method of screening for mantle cell lymphoma in a sample obtained from a subject, the method comprising:
- 1) assaying a methylation state of a DNA methylation marker comprising a chromosomal region having an annotation selected from the group consisting of one of the following groups:
- (i) CACNG8_B, FAM110B, MAX.chr1:61508832-61508969, MAX.chr4.184644069-184644158, and TPBG_C;
- (ii) BNC1_B, FAM110B, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-18464415 8, and MNX1;
- (iii) ADRAID, BNC1_B, CACNG8_B, CDK20_A, FAM110B, GABRG3, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr6.19805195-19805266, MNX1, NRN1_A, SYT6, TPBG_C, and ZNF503;
- and
- (iv) ADRAID, BNC1_B, CACNG8_B, FAM110B, FOXP4, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MNX1, NRN1_A, and TPBG_C, and
- 2) identifying the subject as having mantle cell lymphoma when the methylation state of the marker is different than a methylation state of the marker assayed in a subject that does not have lymphoma.
4 more elements
A method of screening for marginal zone lymphoma in a sample obtained from a subject, the method comprising:
- 1) assaying a methylation state of a DNA methylation marker comprising a chromosomal region having an annotation selected from the group consisting of one of the following groups:
- (i) CACNG8_B, FAM110B, GABRG3, and ITGA5;
- (ii) ADRA1D, BNC1_B, GABRG3, HOXA9, ITGA5, and THBS1;
- (iii) BNC1_B, CACNG8_B, FAM110B, GABRG3, HOXA9, ITGA5, and MAX.chr6.19805195-19805266;
- (iv) ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FOXP4, GABRG3, HOXA9, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, and THBS1;
- and
- (v) CACNG8_B, ADRA1D, TGFB1I1, FAM110B_A, GABRG3, VWA5B1, and ITGA5
- 2) identifying the subject as having marginal zone lymphoma when the methylation state of the marker is different than a methylation state of the marker assayed in a subject that does not have lymphoma.
5 more elements
A method of screening for peripheral T-cell lymphoma in a sample obtained from a subject, the method comprising:
- 1) assaying a methylation state of a DNA methylation marker comprising a chromosomal region having an annotation selected from the group consisting of one of the following groups:
- (i) CACNG8_B, FOXP4, GABRG3, ITGA5, TGFB1I1, and VWASB1;
- (ii) GABRG3, ITGA5, and JUP;
- (iii) ADRA1D, BNC1_B, CACNG8_B, FLRT2, FOXP4, GABRG3, HOXA9, ITGA5, JUP, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, SH3BP4, SYT6, TGFB1I1, and VWASB1;
- (iv) BNC1_B, FOXP4, ITGA5, SH3BP4, SYT6, and TGFB1I1;
- and
- (v) CACNG8_B, ADRA1D, TGFB1I1, FAM110B_A, GABRG3, VWA5B1, and ITGA5
- 2) identifying the subject as having peripheral T-cell lymphoma when the methylation state of the marker is different than a methylation state of the marker assayed in a subject that does not have lymphoma.
5 more elements
A kit comprising:
- 1) a bisulfite reagent;
- and
- 2) a control nucleic acid comprising a sequence from a DMR selected from a group consisting of DMR 1-285 from Tables 1 and/or 3, and having a methylation state associated with a subject who does not have lymphoma.
A kit comprising a bisulfite reagent and an oligonucleotide according to SEQ ID NOS 1-124.
A kit comprising a sample collector for obtaining a sample from a subject;
- reagents for isolating a nucleic acid from the sample;
- a bisulfite reagent;
- and an oligonucleotide according to SEQ ID NOS 1-124.
A composition comprising a nucleic acid comprising a DMR and a bisulfite reagent.
A composition comprising a nucleic acid comprising a DMR and an oligonucleotide according to SEQ ID NOS 1-124.
A composition comprising a nucleic acid comprising a DMR and a methylation-sensitive restriction enzyme.
A composition comprising a nucleic acid comprising a DMR and a polymerase.
A method, comprising:
- measuring a methylation level for one or more genes in a biological sample of a human individual through
- treating genomic DNA in the biological sample with a reagent that modifies DNA in a methylation-specific manner;
- amplifying the treated genomic DNA using a set of primers for the selected one or more genes;
- and
- determining the methylation level of the one or more genes by polymerase chain reaction, nucleic acid sequencing, mass spectrometry, methylation-specific nuclease, mass-based separation, and target capture;
- wherein the one or more genes comprises a chromosomal region having an annotation that is selected from one of the following groups:
- ADRA1D, DNAH14_A, FAMI110B, FAM221A, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644047-184644181, MAX.chr5:74349626-74349841, MAX.chr5:74349626-74349841, MAX.chr6.19805123-19805338, MNX1, NRN1_A, SH3BP4, SYT6, VWA5B1, and ZNF503 (see, Table 2, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FOXP4, ITGA5, JUP, MAX.chr1.61508719-61508998, MAX.chr3.44038141-44038266, TGFB1I1, THBS1, and TPBG_C (see, Table 4, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- ADRA1D, CACNG _B, CDK20_A, DNAH14_A, EBF3_B, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, and SYT6 (see, Table 6, Example I);
- ADRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, and TPBG_C (see, Table 12, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAMI110B, FLRT2, HOXA9, ITGA5, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, TPBG_C, VWA5B1, and ZNF503 (see Table 6, Example I);
- ADRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, FOXP4, GABRG3, HOXA9, MAX.chrl7:79367190-79367336, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, and TPBG_C (see, Table 12, Example I);
- HOXA9, CDK20_B, BNC1_B, DNAH14_B, NRN1_B, SYT2, and CALN1 (see, Table 18, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, THBS1, TPBG_C, and ZNF503 (see, Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, EBF3_B, FAM110B, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TPBG_C, and ZNF503 (see, Table 13, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAMI110B, FLRT2, FOXP4, GABRG3, GATA6, HOXA9, ITGA5, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see, Table 13, Example I);
- MAX.chr5:74349626-74349841, HOXA9, BNC1_B, NRN1_B, TPBG_D, SYT2, and CALN1 (see, Table 18, Example I);
- CACNG8_B, FAM110B, MAX.chr1:61508832-61508969, MAX.chr4.184644069-184644158, and TPBG_C (see, Table 8, Example I);
- BNC1_B, FAM110B, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, and MNX1 (see, Table 14, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FAM110B, GABRG3, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr6.19805195-19805266, MNX1, NRN1_A, SYT6, TPBG_C, and ZNF503 (see Table 8, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FAM110B, FOXP4, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MNX1, NRN1_A, and TPBG_C (see, Table 14, Example I);
- CACNG8_B, FAM110B, GABRG3, and ITGA5 (see, Table 9, Example I);
- ADRA1D, BNC1_B, GABRG3, HOXA9, ITGA5, and THBS1 (see, Table 15, Example I)
- BNC1_B, CACNG8_B, FAM110B, GABRG3, HOXA9, ITGA5, and MAX.chr6.19805195-19805266 (see Table 9, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FOXP4, GABRG3, HOXA9, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, and THBS1 (see, Table 15, Example I);
- CACNG8_B, FOXP4, GABRG3, ITGA5, TGFB1I1, and VWASB1 (see, Table 10, Example I);
- GABRG3, ITGA5, and JUP (see, Table 16, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FLRT2, FOXP4, GABRG3, HOXA9, ITGA5, JUP, MAX.chrl7:79367190-79367336, MAX.chr6.19805195-19805266, SH3BP4, SYT6, TGFB1I1, and VWASB1 (see Table 10, Example I);
- CACNG8_B, ADRA1D, TGFB1I1, FAM110B_A, GABRG3, VWASB1, and ITGA5 (see, Example I);
- and
- BNC1_B, FOXP4, ITGA5, SH3BP4, SYT6, and TGFB1I1 (see, Table 16, Example I).
31 more elements
A method of characterizing a sample, comprising:
- a) measuring an amount of at least one methylated marker gene in DNA extracted from the sample, wherein the one or more genes is selected from one of the following groups:
- ADRA1D, DNAH14_A, FAMI110B, FAM221A, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644047-184644181, MAX.chr5:74349626-74349841, MAX.chr5:74349626-74349841, MAX.chr6.19805123-19805338, MNX1, NRN1_A, SH3BP4, SYT6, VWA5B1, and ZNF503 (see, Table 2, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FOXP4, ITGA5, JUP, MAX.chr1.61508719-61508998, MAX.chr3.44038141-44038266, TGFB1I1, THBS1, and TPBG_C (see, Table 4, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- ADRA1D, CACNG _B, CDK20_A, DNAH14_A, EBF3_B, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, and SYT6 (see, Table 6, Example I);
- ADRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, and TPBG_C (see, Table 12, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAMI110B, FLRT2, HOXA9, ITGA5, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, TPBG_C, VWA5B1, and ZNF503 (see Table 6, Example I);
- ADRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, FOXP4, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, and TPBG_C (see, Table 12, Example I);
- HOXA9, CDK20_B, BNC1_B, DNAH14_B, NRN1_B, SYT2, and CALN1 (see, Table 18, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, THBS1, TPBG_C, and ZNF503 (see, Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, EBF3_B, FAM110B, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TPBG_C, and ZNF503 (see, Table 13, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAMI110B, FLRT2, FOXP4, GABRG3, GATA6, HOXA9, ITGA5, MAX.chr1:61508832-61508969,MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see, Table 13, Example I);
- MAX.chr5:74349626-74349841, HOXA9, BNC1_B, NRN1_B, TPBG_D, SYT2, and CALN1 (see, Table 18, Example I);
- CACNG8_B, ADRA1D, TGFB1I1, FAM110B_A, GABRG3, VWASB1, and ITGA5 (see, Example I);
- ACNG8_B, FAM110B, MAX.chr1:61508832-61508969, MAX.chr4.184644069-184644158, and TPBG_C (see, Table 8, Example I);
- BNC1_B, FAM110B, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, and MNX1 (see, Table 14, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FAM110B, GABRG3, HOXA9, MAX.chr1:61508832-61508969,MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr6.19805195-19805266, MNX1, NRN1_A, SYT6, TPBG_C, and ZNF503 (see Table 8, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FAM110B, FOXP4, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MNX1, NRN1_A, and TPBG_C (see, Table 14, Example I);
- CACNG8_B, FAM110B, GABRG3, and ITGA5 (see, Table 9, Example I);
- ADRA1D, BNC1_B, GABRG3, HOXA9, ITGA5, and THBS1 (see, Table 15, Example I)
- BNC1_B, CACNG8_B, FAM110B, GABRG3, HOXA9, ITGA5, and MAX.chr6.19805195-19805266 (see Table 9, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FOXP4, GABRG3, HOXA9, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, and THBS1 (see, Table 15, Example I);
- CACNG8_B, FOXP4, GABRG3, ITGA5, TGFB1I1, and VWASB1 (see, Table 10, Example I);
- GABRG3, ITGA5, and JUP (see, Table 16, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FLRT2, FOXP4, GABRG3, HOXA9, ITGA5, JUP, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, SH3BP4, SYT6, TGFB1I1, and VWASB1 (see Table 10, Example I);
- and
- BNC1_B, FOXP4, ITGA5, SH3BP4, SYT6, and TGFB1I1 (see, Table 16, Example I);
- b) measuring the amount of at least one reference marker in the DNA;
- and
- c) calculating a value for the amount of the at least one methylated marker gene measured in the DNA as a percentage of the amount of the reference marker gene measured in the DNA, wherein the value indicates the amount of the at least one methylated marker DNA measured in the sample.
29 more elements
A method for characterizing a biological sample comprising:
- measuring an amount of at least one methylated marker gene in DNA extracted from the biological sample, wherein the one or more genes is selected from one of the following groups:
- ADRA1D, DNAH14_A, FAMI110B, FAM221A, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644047-184644181, MAX.chr5:74349626-74349841, MAX.chr5:74349626-74349841, MAX.chr6.19805123-19805338, MNX1, NRN1_A, SH3BP4, SYT6, VWA5B1, and ZNF503 (see, Table 2, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FOXP4, ITGA5, JUP, MAX.chr1.61508719-61508998, MAX.chr3.44038141-44038266, TGFB1I1, THBS1, and TPBG_C (see, Table 4, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- ADRA1D, CACNG _B, CDK20_A, DNAH14_A, EBF3_B, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, and SYT6 (see, Table 6, Example I);
- DRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, and TPBG_C (see, Table 12, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAMI110B, FLRT2, HOXA9, ITGA5, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, TPBG_C, VWA5B1, and ZNF503 (see Table 6, Example I);
- CACNG8_B, ADRA1D, TGFB1I1, FAM110B_A, GABRG3, VWASB1, and ITGA5 (see, Example I);
- ADRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, FOXP4, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, and TPBG_C (see, Table 12, Example I);
- HOXA9, CDK20_B, BNC1_B, DNAH14_B, NRN1_B, SYT2, and CALN1 (see, Table 18, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, THBS1, TPBG_C, and ZNF503 (see, Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, EBF3_B, FAM110B, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TPBG_C, and ZNF503 (see, Table 13, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAMI110B, FLRT2, FOXP4, GABRG3, GATA6, HOXA9, ITGA5, MAX.chr1:61508832-61508969,MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see, Table 13, Example I);
- MAX.chr5:74349626-74349841, HOXA9, BNC1_B, NRN1_B, TPBG_D, SYT2, and CALN1 (see, Table 18, Example I);
- CACNG8_B, FAM110B, MAX.chr1:61508832-61508969, MAX.chr4.184644069-184644158, and TPBG_C (see, Table 8, Example I);
- BNC1_B, FAM110B, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, and MNX1 (see, Table 14, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FAM110B, GABRG3, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr6.19805195-19805266, MNX1, NRN1_A, SYT6, TPBG_C, and ZNF503 (see Table 8, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FAMI110B, FOXP4, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MNX1, NRN1_A, and TPBG_C (see, Table 14, Example I);
- CACNG8_B, FAM110B, GABRG3, and ITGA5 (see, Table 9, Example I);
- ADRA1D, BNC1_B, GABRG3, HOXA9, ITGA5, and THBS1 (see, Table 15, Example I)
- BNC1_B, CACNG8_B, FAM110B, GABRG3, HOXA9, ITGA5, and MAX.chr6.19805195-19805266 (see Table 9, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FOXP4, GABRG3, HOXA9, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, and THBS1 (see, Table 15, Example I);
- CACNG8_B, FOXP4, GABRG3, ITGA5, TGFB1I1, and VWASB1 (see, Table 10, Example I);
- GABRG3, ITGA5, and JUP (see, Table 16, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FLRT2, FOXP4, GABRG3, HOXA9, ITGA5, JUP, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, SH3BP4, SYT6, TGFB1I1, and VWASB1 (see Table 10, Example I);
- and
- BNC1_B, FOXP4, ITGA5, SH3BP4, SYT6, and TGFB1I1 (see, Table 16, Example I);
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using primers specific for a CpG site for each marker gene, wherein the primers specific for each marker gene are capable of binding an amplicon bound by the a primer sequence for the marker gene recited in Table 5, wherein the amplicon bound by the primer sequence for the marker gene recited in Table 5 is at least a portion of a genetic region for the marker gene recited in Tables 1 and/or 3;
- determining the methylation level of the CpG site for one or more genes by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
29 more elements
A method for measuring the methylation level of one or more CpG sites in at least one methylated marker gene in DNA extracted from the biological sample, wherein the one or more genes is selected from one of the following groups:
- ADRA1D, DNAH14_A, FAMI110B, FAM221A, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644047-184644181, MAX.chr5:74349626-74349841, MAX.chr5:74349626-74349841, MAX.chr6.19805123-19805338, MNX1, NRN1_A, SH3BP4, SYT6, VWA5B1, and ZNF503 (see, Table 2, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FOXP4, ITGA5, JUP, MAX.chr1.61508719-61508998, MAX.chr3.44038141-44038266, TGFB1I1, THBS1, and TPBG_C (see, Table 4, Example I);
- BNC1_B, ADRA1D, HOXA9, GABRG3, MAX.chr17:79367190-79367336, FAM110B, TPBG_C, SYT6, MAX.chr6.19805123-19805338, and CACNG8_B (see, Table 11, Example I);
- ADRA1D, CACNG _B, CDK20_A, DNAH14_A, EBF3_B, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, and SYT6 (see, Table 6, Example I);
- ADRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, GABRG3, HOXA9, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, and TPBG_C (see, Table 12, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAHI14_A, EBF3_B, FAM110B, FLRT2, HOXA9, ITGA5, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, TPBG_C, VWA5B1, and ZNF503 (see Table 6, Example I);
- ADRA1D, BNC1_B, CDK20_A, DNAH14_A, FAM110B, FLRT2, FOXP4, GABRG3, HOXA9, MAX.chrl7:79367190-79367336, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, and TPBG_C (see, Table 12, Example I);
- HOXA9, CDK20_B, BNC1_B, DNAH14_B, NRN1_B, SYT2, and CALN1 (see, Table 18, Example I);
- CACNG8_B, ADRA1D, TGFB1I1, FAM110B_A, GABRG3, VWASB1, and ITGA5 (see, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, THBS1, TPBG_C, and ZNF503 (see, Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, EBF3_B, FAM110B, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TPBG_C, and ZNF503 (see, Table 13, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, DNAH14_A, EBF3_B, FAM110B, FLRT2, FOXP4, GABRG3, GATA6, HOXA9, ITGA5, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see Table 7, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, EBF3_B, FAM110B, FLRT2, GABRG3, GATA6, HOXA9, MAX.chr17:79367190-79367336, MAX.chr5:74349626-74349841, MAX.chr6.19805195-19805266, NRN1_A, SH3BP4, SYT6, TGFB1I1, THBS1, TPBG_C, and ZNF503 (see, Table 13, Example I);
- MAX.chr5:74349626-74349841, HOXA9, BNC1_B, NRN1_B, TPBG_D, SYT2, and CALN1 (see, Table 18, Example I);
- CACNG8_B, FAM110B, MAX.chr1:61508832-61508969, MAX.chr4.184644069-184644158, and TPBG_C (see, Table 8, Example I);
- BNC1_B, FAM110B, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, and MNX1 (see, Table 14, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FAM110B, GABRG3, HOXA9, MAX.chr1:61508832-61508969, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MAX.chr6.19805195-19805266, MNX1, NRN1_A, SYT6, TPBG_C, and ZNF503 (see Table 8, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FAM110B, FOXP4, HOXA9, MAX.chr17:79367190-79367336, MAX.chr4.184644069-184644158, MNX1, NRN1_A, and TPBG_C (see, Table 14, Example I);
- CACNG8_B, FAM110B, GABRG3, and ITGA5 (see, Table 9, Example I);
- ADRA1D, BNC1_B, GABRG3, HOXA9, ITGA5, and THBS1 (see, Table 15, Example I)
- BNC1_B, CACNG8_B, FAM110B, GABRG3, HOXA9, ITGA5, and MAX.chr6.19805195-19805266 (see Table 9, Example I);
- ADRA1D, BNC1_B, CACNG8_B, CDK20_A, FOXP4, GABRG3, HOXA9, MAX.chr5:74349626-74349841, NRN1_A, SH3BP4, and THBS1 (see, Table 15, Example I);
- CACNG8_B, FOXP4, GABRG3, ITGA5, TGFB1I1, and VWASB1 (see, Table 10, Example I);
- GABRG3, ITGA5, and JUP (see, Table 16, Example I);
- ADRA1D, BNC1_B, CACNG8_B, FLRT2, FOXP4, GABRG3, HOXA9, ITGA5, JUP, MAX.chr17:79367190-79367336, MAX.chr6.19805195-19805266, SH3BP4, SYT6, TGFB1I1, and VWASB1 (see Table 10, Example I);
- and
- BNC1_B, FOXP4, ITGA5, SH3BP4, SYT6, and TGFB1I1 (see, Table 16, Example I);
- comprising;
- a) extracting genomic DNA from a biological sample of a human individual suspected of having or having a neoplasm, wherein the neoplasm is NHL or a subtype or NHL;
- b) treating the extracted genomic DNA with bisulfite,
- c) amplifying the bisulfite-treated genomic DNA with primers specific for the one or more genes, wherein the primers specific for the one or more genes are capable of binding at least a portion of the bisulfite-treated genomic DNA for a chromosomal region for the marker recited in Tables 1 and/or 3;
- and
- d) measuring the methylation level of one or more CpG sites by methylation-specific PCR, quantitative methylation-specific PCR, methylation sensitive DNA restriction enzyme analysis or bisulfite genomic sequencing PCR.
31 more elements
A method for characterizing a biological sample comprising:
- measuring a methylation level of a CpG site for one or more of markers shown in Tables 1 and/or 3 in a biological sample of a human individual through
- treating genomic DNA in the biological sample with bisulfite;
- amplifying the bisulfite-treated genomic DNA using primers specific for the one or more markers shown in Tables 1 and/or 3, wherein the primers specific for each of the markers shown in Tables 1 and/or 3 are capable of binding an amplicon bound by a respective primer pair sequence shown in Table 5, wherein the amplicon bound by the respective primer pair sequence shown in Table 5 is at least a portion of a genetic region comprising the respective chromosomal coordinates shown in Tables 1 and/or 3;
- determining the methylation level of the CpG site for the markers shown in Tables 1 and/or 3 by methylation-specific PCR, quantitative methylation-specific PCR, methylation-sensitive DNA restriction enzyme analysis, quantitative bisulfite pyrosequencing, or bisulfite genomic sequencing PCR.
1 more element
Dependencies are inferred from the claim text.