Methods for predicting tumor content using epigenetic signatures
AssigneeFlagship Pioneering Innovations VI, LLC
InventorsJocelyn Charlton, James Xin Sun, Caitlin M. Gilley
Life of this patent
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Abstract
Disclosed herein are methods and compositions for predicting tumor content e.g., tumor content in a sample and tumor burden of an individual. Generally, methods and compositions involve determining methylation statuses of two or more sequential CpG sites in one or more genomic locations using nucleic acids of the obtained sample. The methylation statuses of the two or more sequential CpG in genomic locations are used to distinguish between reads of nucleic acids that are likely derived from cancer and reads of other nucleic acids that are unlikely to be derived from cancer. Distinguishing reads that are likely derived from cancer enables the prediction of tumor content in a sample.
Claims24
A method of determining tumor DNA content in a biological sample comprising:
- a) obtaining cell-free DNA fragments from the sample;
- b) determining methylation statuses of methylation variants each representing two or more sequential CpG sites in a genomic location from the cell-free DNA fragments;
- and
- c) quantifying a proportion of fully methylated methylation variants,
- wherein the quantification in step c) is performed without requiring a matched tissue sample.
(canceled)
14-35. (canceled)
A method of determining tumor DNA content in a biological sample comprising:
- a) obtaining cell-free DNA fragments from the sample;
- b) determining methylation statuses of methylation variants each representing two or more sequential CpG sites in a genomic location from the cell-free DNA fragments;
- and
- c) quantifying a proportion of fully methylated methylation variants,
- wherein the cell-free DNA fragments are detected with a sensitivity of at least 85% when the proportion of the cell-free DNA fragments in which the sequential CpG sites of the genomic locations are methylated is greater than 0.0001.
43-135. (canceled)
A method of identifying a subject as a candidate subject for treatment, the method comprising:
- a) performing longitudinal tracking of tumor content across two or more samples obtained from the subject, wherein the performing comprises:
- i) obtaining cell-free DNA fragments from a sample obtained from a subject at a timepoint;
- ii) determining methylation statuses of methylation variants each representing two or more sequential CpG sites in a genomic location from the cell-free DNA fragments;
- iii) quantifying a proportion of fully methylated methylation variants without requiring a matched tissue sample;
- iv) determining whether the sample is positive for cancer if the proportion of fully methylated methylation variants relative to a total number of methylation variants is greater than a threshold proportion;
- v) repeating steps (i)-(iv) for an additional sample of the two or more samples obtained from the subject at a different timepoint;
- and
- f) determining a total number or proportion of samples of the two or more samples that are positive for cancer;
- and
- g) responsive to determining that at least a threshold of the two or more samples are positive for cancer, identifying the subject as a candidate subject for treatment.
137-159. (canceled)
Dependencies are inferred from the claim text.