US 11,834,718 B2
Compositions and methods for diagnosing, evaluating and treating cancer by means of the DNA methylation status
Mark Kendell Clement, Cambridge, MA (US); Gad Getz, Cambridge, MA (US); Dan-Avi Landau, Cambridge, MA (US); Alexander Meissner, Brookline, MA (US); and Catherine Ju-Ying Wu, Brookline, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); Dana-Farber Cancer Institute, Inc., Boston, MA (US); The General Hospital Corporation, Boston, MA (US); and President and Fellows of Harvard College, Cambridge, MA (US)
Filed by The Broad Institute, Inc., Cambridge, MA (US); Dana-Farber Cancer Institute, Inc., Boston, MA (US); The General Hospital Corporation, Boston, MA (US); and President and Fellows of Harvard College, Cambridge, MA (US)
Filed on Sep. 10, 2020, as Appl. No. 17/017,045.
Application 17/017,045 is a division of application No. 15/038,504, granted, now 10,801,070, issued on Oct. 13, 2020, previously published as PCT/US2014/067146, filed on Nov. 24, 2014.
Claims priority of provisional application 61/908,316, filed on Nov. 25, 2013.
Prior Publication US 2020/0407804 A1, Dec. 31, 2020
Int. Cl. C12Q 1/6886 (2018.01); C12Q 1/6869 (2018.01); G16B 30/00 (2019.01); G16B 30/10 (2019.01)
CPC C12Q 1/6886 (2013.01) [C12Q 1/6869 (2013.01); G16B 30/00 (2019.02); G16B 30/10 (2019.02); C12Q 2600/106 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/154 (2013.01); C12Q 2600/156 (2013.01)] 10 Claims
 
1. A method of treating cancer in a subject comprising calculating a proportion of discordant reads (PDR) in a tumor sample from the subject comprising:
detecting DNA methylation status by massive parallel sequencing with bisulfite conversion; whole-genome bisulfite sequencing; reduced representation bisulfite sequencing; microarray, or a genome-wide microarray at one or more regions of neighboring CpG sites in a plurality of cells in the tumor sample;
comparing the DNA methylation status in multiple regions of neighboring CpG sites along a sequence of CpG sites in DNA of the plurality of cells; and
determining a relative number of cells in the tumor sample having inconsistent DNA methylation status across the sequence of CpG sites as compared to the total number of cells in the tumor sample or a number of cells in the tumor sample having consistent DNA methylation status across the sequence of CpG sites thereby calculating the PDR in the tumor sample,
determining the PDR in the tumor sample to be less than or equal to 0.15, and
administering to the subject an antitumor agent.