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 system for determining a cell free DNA (cfDNA) fragmentation profile of a subject comprising:
 processing cfDNA fragments obtained from a sample obtained from the subject into sequencing libraries;   subjecting the sequencing libraries to whole genome sequencing to obtain sequenced fragments, wherein genome coverage is from about 0.1× to 9×;   mapping the sequenced fragments to a genome to obtain genomic intervals of mapped sequences;   analyzing the genomic intervals of mapped sequences to determine cfDNA fragment lengths; and   determining a cfDNA fragmentation profile for the subject.   
     
     
         69 . The system of  claim 68 , wherein the system is a machine learning system. 
     
     
         70 . The system of  claim 69 , wherein the machine learning system is a gradient tree boosting machine learning system. 
     
     
         71 . The system of  claim 68 , wherein a cfDNA fragmentation profile in the subject that is more variable than a reference cfDNA fragmentation profile is indicative of the subject as having or at risk of having cancer. 
     
     
         72 . The system of  claim 68 , wherein a cfDNA fragmentation profile in the subject that is less or equally variable than a reference cfDNA fragmentation profile is indicative of the subject as being healthy. 
     
     
         73 . The system of  claim 71 , wherein the reference cfDNA fragmentation profile is a reference nucleosome cfDNA fragmentation profile. 
     
     
         74 . The system of  claim 68 , wherein determining the cfDNA fragmentation profile distinguishes circulating tumor DNA (ctDNA) from non-cancer-associated white blood cell DNA in the blood. 
     
     
         75 . The system of  claim 68 , wherein the mapped sequences comprise tens or hundreds to thousands of genomic intervals. 
     
     
         76 . The system of  claim 68 , wherein the genomic intervals are non-overlapping. 
     
     
         77 . The system of  claim 68 , wherein the genomic intervals each comprise thousands to millions of base pairs. 
     
     
         78 . The system of  claim 68 , wherein a cfDNA fragmentation profile is determined within each genomic interval. 
     
     
         79 . The system of  claim 68 , wherein a cfDNA fragmentation profile comprises a median fragment size. 
     
     
         80 . The system of  claim 68 , wherein a cfDNA fragmentation profile comprises a fragment size distribution. 
     
     
         81 . The system of  claim 68 , wherein a cfDNA fragmentation profile is determined over the whole genome or a subgenomic interval. 
     
     
         82 . The system of  claim 68 , wherein cfDNA fragmentation profiles provide over 20,000 reads per genomic intervals. 
     
     
         83 . The system of  claim 68 , wherein the genomic coverage is about 0.1×, 0.2×, 0.5×, 1× or 2×. 
     
     
         84 . The system of  claim 68 , wherein the cfDNA fragmentation profile further predicts the tissue of origin of the cancer in a subject having or at risk of having cancer. 
     
     
         85 . The system of  claim 68 , wherein the cancer is selected from the group consisting of: colorectal cancer, lung cancer, breast cancer, gastric cancer, pancreatic cancer, bile duct cancer, and ovarian cancer. 
     
     
         86 . The system of  claim 68 , wherein the cancer is treated with or has previously been treated with a treatment comprising administering to the subject a cancer treatment selected from the group consisting of surgery, adjuvant chemotherapy, neoadjuvant chemotherapy, radiation therapy, hormone therapy, cytotoxic therapy, immunotherapy, adoptive T cell therapy, targeted therapy and combination thereof. 
     
     
         87 . The system of  claim 68 , wherein cfDNA fragments are nucleosome protected DNA fragments. 
     
     
         88 . The system of  claim 68 , wherein the sample is a blood, serum, plasma, amnion, tissue, urine, cerebrospinal fluid, saliva, sputum, broncho-alveolar lavage, bile, lymphatic fluid, cyst fluid, stool, ascites, pap smear, breast milk or exhaled breath condensate sample. 
     
     
         89 . A method of predicting a cell free DNA (cfDNA) fragmentation profile of a subject comprising:
 determining a cfDNA fragmentation profile prediction for the subject based on a DNA evaluation of fragments for early interception (DELFI) classifier score, using the system of  claim 68 , thereby predicting a cfDNA fragmentation profile of the subject.   
     
     
         90 . A method of predicting a cancer status in a subject comprising:
 determining a cfDNA fragmentation profile prediction for the subject using the system of  claim 68 ; and   classifying the subject as a healthy subject or a subject having or at risk of having cancer based on variability of the cfDNA fragmentation profile in the subject, thereby predicting a cancer status in the subject.   
     
     
         91 . A method of detecting and/or monitoring the status of cancer in a subject comprising:
 determining a first cfDNA fragmentation profile of the subject at a first time using the system of  claim 68 ; and   classifying the subject as a healthy subject or a subject having or at risk of having cancer based on the cfDNA fragmentation profile of the subject, thereby detecting cancer in the subject.   
     
     
         92 . The method of  claim 91 , further comprising determining a second cfDNA fragmentation profile of the subject at a second time and comparing the first cfDNA fragmentation profile to the second cfDNA fragmentation profile to monitor the status of cancer in the subject. 
     
     
         93 . The method of  claim 92 , wherein the first and/or the second cfDNA fragmentation profiles are determined before, during and/or after the course of a cancer treatment. 
     
     
         94 . The method of  claim 93 , wherein determining the first and/or the second cfDNA fragmentation profiles over the course of a cancer treatment indicates responsiveness to the cancer treatment. 
     
     
         95 . The method of  claim 92 , wherein a second cfDNA fragmentation profile that is less or equally variable than a reference cfDNA fragmentation profile obtained in a healthy subject indicates a response to the cancer treatment in the subject. 
     
     
         96 . The method of  claim 92 , wherein a second cfDNA fragmentation profile that is more variable than a reference cfDNA fragmentation profile obtained in a healthy subject indicates an absence of response to the cancer treatment in the subject. 
     
     
         97 . The method of  claim 91 , wherein determining the cfDNA fragmentation profile is indicative of a change in tumor size, and/or change in tumor localization.