Cell-free dna for assessing and/or treating cancer

Abstract

This document relates to methods and materials for assessed, monitored, and/or treated mammals (e.g., humans) having cancer. For example, methods and materials for identifying a mammal as having cancer (e.g., a localized cancer) are provided. For example, methods and materials for assessing, monitoring, and/or treating a mammal having cancer are provided.

1 - 67 . (canceled) 
     
     
         68 . A method of determining the cancer status of a subject comprising:
 using a machine learning model, determining the existence of a change in chromosomal arm DNA copy number from a sample of cfDNA from the subject relative to a reference and classifying the subject as having cancer when there is change in the copy number of chromosomal arm DNA relative to the reference.   
     
     
         69 . The method of  claim 68 , wherein the chromosome arm copy number change is determined by a score relative to a reference. 
     
     
         70 . The method of  claim 68 , further comprising:
 determining the change in chromosome copy number from a cell free DNA (cfDNA) fragmentation profile in a sample obtained from the subject;   comparing the cfDNA fragmentation profile to a reference cfDNA fragmentation profile; and   identifying the subject as having cancer when the cfDNA fragmentation profile obtained from the subject is different from the reference cfDNA fragmentation profile.   
     
     
         71 . The method of  claim 70 , wherein the reference cfDNA fragmentation profile is a cfDNA fragmentation profile of a at least one mammal without cancer. 
     
     
         72 . The method of  claim 71 , wherein the reference cfDNA fragmentation profile is generated by determining a cfDNA fragmentation profile in a sample obtained from the at least one mammal without cancer. 
     
     
         73 . The method of  claim 68 , wherein the cancer is selected from the group consisting of colorectal cancer, lung cancer, breast cancer, gastric cancers, pancreatic cancers, bile duct cancers, and ovarian cancer. 
     
     
         74 . The method of  claim 70 , comprising processing cfDNA fragments obtained from the sample obtained from the subject into sequencing libraries. 
     
     
         75 . The method of  claim 74 , wherein the sequencing libraries are subjected to whole genome sequencing to obtain sequenced fragments, wherein genome coverage is about 9× to 0.1×. 
     
     
         76 . The method of  claim 70 , wherein the cfDNA fragmentation profile comprises the sequence coverage of cfDNA fragments in chromosome arms. 
     
     
         77 . The method of  claim 76 , wherein genome coverage is from about 2×, 1×, 0.5×, 0.2× or 0.1×. 
     
     
         78 . The method of  claim 70  wherein the cfDNA fragmentation profile is over the whole genome or a subgenomic interval. 
     
     
         79 . The method of  claim 69 , wherein the score is a Z score. 
     
     
         80 . The method of  claim 68 , wherein the change in copy number in chromosome arms is one feature in a multi-feature classifier using additional features. 
     
     
         81 . The method of  claim 80 , wherein at least one additional feature is derived from a fragmentation profile. 
     
     
         82 . The method of  claim 81 , wherein the additional features include one or more of: a ratio of small cfDNA fragments to large cfDNA fragments, a fragment size distribution, a median fragment size, mitochondrial mapping. 
     
     
         83 . The method of  claim 82 , wherein one or more of the additional features are calculated from defined informative windows of mapped sequences in the genome.