US 12,391,995 B2
Epigenetic markers and related methods and means for the detection and management of certain cancers
Martin Widschwendter, Wildermieming (AT); Allison Jones, London (GB); Iona Evans, London (GB); Harri Lempiäinen, Binningen (CH); Johannes Eichner, Lörrach (DE); Tamas Rujan, Oberwil (CH); Timo Wittenberger, Constance (DE); Tobias Paprotka, Leipzig (DE); and Benjamin Lindner, Laupheim (DE)
Assigned to Eurofins Genomics Europe Sequencing GmbH, Constance (DE); Genedata AG, Basel (CH); and UCL Business Ltd., London (GB)
Filed by EUROFINS GENOMICS EUROPE SEQUENCING GMBH, Constance (DE); GENEDATA AG, Basel (CH); and UCL BUSINESS LTD., London (GB)
Filed on Jan. 22, 2024, as Appl. No. 18/418,913.
Application 18/418,913 is a continuation of application No. 16/469,963, granted, now 11,920,200, previously published as PCT/EP2017/083170, filed on Dec. 15, 2017.
Claims priority of application No. 16204822 (EP), filed on Dec. 16, 2016.
Prior Publication US 2024/0200142 A1, Jun. 20, 2024
Int. Cl. C12Q 1/6886 (2018.01); G16B 20/00 (2019.01); G16B 40/10 (2019.01); G16H 20/00 (2018.01); G16H 50/20 (2018.01)
CPC C12Q 1/6886 (2013.01) [G16B 20/00 (2019.02); G16B 40/10 (2019.02); G16H 20/00 (2018.01); G16H 50/20 (2018.01); C12Q 2600/106 (2013.01); C12Q 2600/112 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/154 (2013.01)] 13 Claims
 
1. A method of determining the presence of, or a reduced response to a carboplatin therapy against, a cancer in a human individual, said method comprising the steps:
isolating cell-free DNA from a serum or plasma sample from said human individual;
treating said cell-free DNA with bisulfite that differentially modifies said cell-free DNA based on the methylation status of CpGs in the cell-free DNA;
bisulfite sequencing said modified cell-free DNA;
determining, in at least one molecule of said cell-free DNA using a computer, the methylation status at 7 CpGs located at positions 37, 42, 44, 60, 68, 77 and 86 within the nucleotide sequence of SEQ ID NO:3 (DMR #228) or a 100% complementary sequence of said nucleotide sequence and optionally at 11 CpGs located at positions 28, 31, 34, 48, 54, 67, 70, 82, 88, 101 and 104 within the nucleotide sequences of SEQ ID NO:4 (DMR #144), or a 100% complementary sequence of said nucleotide sequence(s);
determining the presence of the cancer in said human individual, or the reduced response to said carboplatin therapy against the cancer in said human individual when at least one molecule of said cell-free DNA is methylated at each of said 7 CpGs within the nucleotide sequence of SEQ ID NO: 3 and optionally at each of said 11 CpGs within the nucleotide sequence of SEQ ID NO: 4; and
treating the cancer in said human individual by (i) administering a chemotherapeutic agent selected from the group consisting of paclitaxel, docetaxel, cisplatin, liposomal doxorubicin, gemcitabine, trabectedin, etoposide, cyclophosphamide an angiogenesis inhibitor and a PARP inhibitor, or (ii) by performing tumor de-baulking surgery;
wherein: (a) when the human individual is a woman the cancer is selected from the group consisting of: breast cancer, lung cancer, colon cancer, pancreatic cancer, uterine (endometrial) cancer, cervical cancer and ovarian cancer; or (b) when the human individual is a man the cancer is selected from the group consisting of: lung cancer, colon cancer, pancreatic cancer and prostate cancer.