SYSTEMS AND METHODS OF SCORING RISK AND RESIDUAL DISEASE FROM PASSENGER MUTATIONS
In particular, systems and methods of the invention measure amounts of passenger mutations, and optionally driver mutations, to predict risk of cancer-related pathogenicity. Preferably, the mutations are measured from sequences reads. Sequence reads of patient-derived nucleic acids may be compared with one or more references to identify and measure the amount of passenger mutations and optionally driver mutations. The amount of passenger and driver mutations may be correlated to known associations with recurrent and residual disease to predict a risk of cancer recurrence.
1 . A method for predicting risk of recurrent or residual cancer, the method comprising the steps of:
measuring an amount of one or more passenger mutations from nucleic acids;
correlating said amount of passenger mutations with known associations with residual or recurrent disease; and
predicting risk of recurrent or residual disease based upon said correlating step.
2 . The method of claim 1 , further comprising measuring one or more driver mutations from the nucleic acids and including the measured driver mutations in the correlating step.
3 . The method of claim 1 , wherein the nucleic acids are isolated from a blood sample from a patient.
4 . The method of claim 1 , further comprising the step of determining an expression level for one or more gene transcripts and including the determined expression levels in the predicting step.
5 . The method of claim 1 , further comprising the step of assessing disease severity based on the correlating step.
6 . The method of claim 3 , wherein the nucleic acids comprise cell free nucleic acids.
7 . The method of claim 6 , wherein the cell free nucleic acids comprise ctDNA.
8 . The method of claim 7 , wherein said measuring step comprises sequencing the cell free nucleic acid to produce a plurality of sequence reads.
9 . The method of claim 8 , further comprising the step of analyzing the plurality of sequence reads, wherein analyzing comprises detecting one or more passenger mutations previously identified in a first patient assay.
10 . The method of claim 9 , wherein the first patient assay was performed at least one month before performing the steps of the method.
11 . The method of claim 10 , wherein the steps of the method are performed after the patient received a treatment and the first patient assay was performed before said treatment.
12 . The method of claim 8 , further comprising identifying and recording locations of the one or more passenger mutations from the sequence reads and storing the locations in a data file for use in a future patient assay.
13 . The method of claim 1 , wherein the nucleic acids comprise RNA.
14 . The method of claim 1 , further comprising the step of enriching for chromosomal regions having at least one passenger mutation previously identified in a first patient assay and measuring one or more passenger mutations in those chromosomal regions.
15 . The method of claim 14 , wherein enriching comprises using hybridization probes to capture and isolate chromosomal regions having at least one passenger mutation.
16 . The method of claim 1 , wherein the passenger mutations comprise mutations that do not show a significant statistical correlation with breast cancer.