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AssigneesUCL Business PLC, Eurofins Genomics Europe Sequencing GMBH, Genedata AG
InventorsMartin Widschwendter, Allison Jones, Iona Evans, Harri Lemppiainen, Johannes Eichner, Tamas Rujan, Timo Wittenberger, Tobias Paprotka, Benjamin Lindner
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The present invention relates to methods of identifying the presence of DNA from one or more metastatic breast cancer (mBC) cells in a sample from an individual. The invention also relates to methods of diagnosing metastatic breast cancer (mBC) by identifying the presence of mBC cell DNA in a sample from an individual. The invention also relates to methods of identifying a breast cancer patient as having a poor disease prognosis by identifying the presence of DNA from one or more mBC cells in a sample from an individual. The invention additionally relates to methods of identifying in DNA from an individual the presence of a methylation signature associated with mBC by identifying the presence of DNA from one or more mBC cells in a sample from an individual. The invention also relates to oligonucleotide primers for amplifying differentially methylated regions (DMRs) and/or methylation variable positions (MVPs), detection probes for detecting amplicons comprising DMRs and MVPs and kits comprising oligonucleotide primers, detection probes and reagents for use in the methods of the invention.
A method of identifying the presence of metastatic breast cancer (mBC) cell DNA in a sample from an individual, the method comprising:
A method of diagnosing metastatic breast cancer (mBC) by identifying the presence of mBC cell DNA in a sample from an individual, the method comprising:
A method of providing a disease prognosis to a breast cancer patient by identifying the presence of metastatic breast cancer (mBC) cell DNA in a sample from an individual, the method comprising:
A method of identifying in DNA from an individual the presence of a methylation signature correlated with metastatic breast cancer (mBC) by identifying the presence of mBC DNA in a sample from an individual, the method comprising:
A method according to any one of the preceding claims, wherein in step (v) the DMR methylation pattern frequency threshold value is 0.0001, or 0.0002, or 0.0003, or 0.0004, or 0.0005, or 0.0006, or 0.0007, or 0.0008, or 0.0009, or 0.001, preferably 0.0008.
A method according to any one of the preceding claims, wherein the method achieves a ROC sensitivity of 60% or more.
A method according to any one of the preceding claims, wherein the method achieves a ROC specificity of 90% or more.
A method according to any one of the preceding claims, wherein the method achieves a ROC sensitivity of 60% or more and a ROC specificity of 90% or more, preferably wherein the method achieves a ROC sensitivity of 60.9% or more and a ROC specificity of 92% or more.
A method according to any one of claims 121 to 123, wherein in step (iii) the methylation pattern is defined to score as methylated each MVP in a group of MVPs comprising the MVPs of SEQ ID NOS:
A method according to any one of the preceding claims, wherein for a given DMR the step of determining the methylation status of MVPs and the step of selecting a DMR methylation pattern for MVPs is performed by a single process, the process comprising the steps of:
A method according to any one of the preceding claims, wherein the sample from the individual is a sample of serum, preferably wherein sample DNA is cell-free DNA obtained following removal of cells from serum.
A method of treating a patient having metastatic breast cancer (mBC) comprising identifying mBC DNA within a sample from the individual by performing the method of any one of the preceding claims and providing one or more cancer treatments to the patient.
A detection probe comprising an isolated oligonucleotide molecule and a detection system, wherein the probe is designed to anneal to a site comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
A detection probe comprising an isolated oligonucleotide molecule and a detection system, wherein the probe is designed to anneal to a site comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
An isolated oligonucleotide molecule for use as an amplification primer, wherein the molecule is designed to anneal to a site comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
An isolated oligonucleotide molecule for use as an amplification primer, wherein the molecule is designed to anneal to a site comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
A pair of isolated oligonucleotide molecules for use as forward and reverse amplification primers, wherein one or both of the molecules are designed to anneal to a site comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
A pair of isolated oligonucleotide molecules for use as forward and reverse amplification primers, wherein one or both of the molecules are designed to anneal to a site comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
An isolated oligonucleotide molecule for use as an amplification primer, wherein the molecule is designed to anneal to a site adjacent to a DNA region comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
An isolated oligonucleotide molecule for use as an amplification primer, wherein the molecule is designed to anneal to a site adjacent to a DNA region comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
A pair of isolated oligonucleotide molecules for use as forward and reverse amplification primers, wherein one or both of the molecules are designed to anneal to a site adjacent to a DNA region comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
A pair of isolated oligonucleotide molecules for use as forward and reverse amplification primers, wherein one or both of the molecules are designed to anneal to a site adjacent to a DNA region comprising one or more of the MVPs of or corresponding to SEQ ID NOS:
An isolated oligonucleotide molecule for use as a forward or reverse amplification primer, wherein the molecule is designed to anneal to a site in a DMR and to be capable of amplifying the DMR or a region of the DMR when used with a corresponding reverse or forward amplification primer, wherein the DMR is a DMR having a sequence set forth in any one of SEQ ID NOS:
A pair of isolated oligonucleotide molecules for use as forward and reverse amplification primers, wherein the molecules are designed to amplify a DMR or wherein the molecules are designed to amplify a region of a DMR, wherein the DMR is a DMR having a sequence set forth in any one of SEQ ID NOS:
Dependencies are inferred from the claim text.