Classification of diffuse large b-cell lymphoma
AssigneesTrustees of Boston University, Dana-Farber Cancer Institute, Inc.
InventorsStefano MONTI, Daniel GUSENLEITNER, Margaret SHIPP, Bjoern CHAPUY
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Abstract
Disclosed are methods and reagents for diagnosis, classification and treatment of DLBCL and subtypes thereof by means of gene expression profiling. Provided herein is a gene expression signature for use in obtaining diagnostic information for DLBCL and subtypes thereof. Aspects of the present disclosure relate to use of gene expression signature corresponding to particular subtype for classification of a sample from a subject and stratification of a subject for subtype-targeted clinical trial. Also provided herein is a computer based classification model for use in the methods disclosed herein.
Claims27
A method of treating a subject for cancer, the method comprising:
- a. assaying a sample from a cancer cell of the subject, for levels of gene expression of at least four genes from genes of SEQ ID NOs 1-141 or a subset thereof;
- b. normalizing the assayed levels of gene expression with a control;
- c. identifying the genes whose assayed levels of expression are upregulated;
- d. administering a therapeutic regimen for the treatment of cancer of the BCR subtype if the expression of at least two of the group consisting of TRMU, CKAP5, PLCG2, FUS, WEE1, ITPR3, SNRPA, PKMYT1, and SUPT5H are identified to be upregulated;
- or
- e) administering a therapeutic regimen for the treatment of cancer of the Host Receptor subtype if the expression of at least two genes of the group consisting of PD-L1, CTLA4, IL15RA, GNS, PTPRM, AMICA, CFH, CD2, ITGAL, ACTN1, A2M and IL2RB are identified to be upregulated;
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- f) administering a therapeutic regimen for the treatment of cancer of the OxPhos subtype if the expression of at least two of the group consisting of SPCS3, SUCLG1, NDUFAB1, FADD, MRPS16, ATP6V1D, NDUFB1, NDUFB3, SEC11A and PARK7 are identified to be upregulated.
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A kit comprising a plurality of probes for determining levels of gene expression of genes of SEQ ID NOs 1-141 or a subset thereof, wherein the subset comprises at least four genes selected from group consisting of TRMU, CKAP5, PLCG2, FUS, WEE1, ITPR3, SNRPA, PKMYT1, and SUPT5H, or at least {two} genes selected from group consisting of PD-L1, CTLA4, IL15RA, GNS, PTPRM, AMICA, CFH, CD2, ITGAL, ACTN1, A2M and IL2RB, or at least three genes selected from group consisting of SPCS3, SUCLG1, NDUFAB1, FADD, MRPS16, ATP6V1D, NDUFB1, NDUFB3, SEC11A and PARK7.
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A computer readable medium or computer program product comprising a classifier that predicts the DLBCL-subtype, based on weighted expression of genes of SEQ ID NOs 1-141 or a subset thereof in a sample from a subject having or suspected of having DLBCL, wherein the subset comprises at least four genes selected from group consisting of TRMU, CKAP5, PLCG2, FUS, WEE1, ITPR3, SNRPA, PKMYT1, and SUPT5H and at least {two} genes selected from group consisting of PD-L1, CTLA4, IL15RA, GNS, PTPRM, AMICA, CFH, CD2, ITGAL, ACTN1, A2M and IL2RB and at least three genes selected from group consisting of SPCS3, SUCLG1, NDUFAB1, FADD, MRPS16, ATP6V1D, NDUFB1, NDUFB3, SEC11A and PARK7, said classifier having been trained by in silico analysis and classification algorithms.
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Dependencies are inferred from the claim text.