US 11,884,966 B2
Tissue-specific methylation marker
Yuk-Ming Dennis Lo, Hong Kong (CN); Rossa Wai Kwun Chiu, Hong Kong (CN); Kwan Chee Chan, Hong Kong (CN); Wanxia Gai, Hong Kong (CN); and Lu Ji, Hong Kong (CN)
Assigned to GRAIL, LLC, Menlo Park, CA (US)
Filed by GRAIL, LLC, Menlo Park, CA (US)
Filed on Mar. 15, 2019, as Appl. No. 16/354,799.
Claims priority of provisional application 62/769,928, filed on Nov. 20, 2018.
Claims priority of provisional application 62/643,649, filed on Mar. 15, 2018.
Prior Publication US 2019/0390257 A1, Dec. 26, 2019
Int. Cl. C12Q 1/68 (2018.01); C12Q 1/6823 (2018.01); C12Q 1/6886 (2018.01)
CPC C12Q 1/6823 (2013.01) [C12Q 1/6886 (2013.01); C12Q 2600/112 (2013.01); C12Q 2600/118 (2013.01); C12Q 2600/154 (2013.01); C12Q 2600/156 (2013.01); C12Q 2600/158 (2013.01); C12Q 2600/172 (2013.01)] 20 Claims
 
1. A method of detecting and treating a metastasis in a subject, the method comprising selecting a subject having a metastasis of a cancer with a tissue of origin, and administering a treatment to the subject effective to treat the metastasis, wherein:
(a) the selecting comprises (i) receiving results of an assay of a first biological sample of the subject measuring an absolute amount of cell-free DNA comprising a target sequence having a first methylation status (ii) identifying the measured absolute amount as being above a reference amount, and (iii) identifying a first non-cancer tissue as a location of the metastasis;
(b) the first biological sample comprises cell-free DNA molecules from the cancer, the first non-cancer tissue, and one or more second non-cancer tissues;
(c) the tissue of origin, the first non-cancer tissue, and the one or more second non-cancer tissues are different;
(d) cell-free DNA molecules from the first non-cancer tissue comprise the first methylation status of the target sequence;
(e) the first methylation status is distinct from one or more second methylation statuses of the target sequence in cell-free DNA molecules from the cancer and from the one or more second non-cancer tissues;
(f) the reference amount is an absolute amount of cell-free DNA comprising the target sequence having the first methylation status for one or more subjects without metastasis in the first non-cancer tissue; and
(g) the treatment is selected from the group consisting of chemotherapy, radiation therapy, surgical removal of tumor tissues, immunotherapy, hormone therapy, and stem cell therapy.