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 . A method of determining a cell free DNA (cIDNA) fragmentation profile of a mammal, the method comprising:
 processing cfDNA fragments obtained from a sample obtained from the mammal into sequencing libraries;   subjecting the sequencing libraries to low-coverage whole genome sequencing to obtain sequenced fragments;   mapping the sequenced fragments to a genome to obtain windows of mapped sequences; and   analyzing the windows of mapped sequences to determine cfDNA fragment lengths.   
     
     
         2 . The method of  claim 1 , wherein the mapped sequences comprise tens to thousands of windows. 
     
     
         3 . The method of  claim 1 , wherein the windows are non overlapping windows. 
     
     
         4 . The method of  claim 1 , wherein the windows each comprise about 5 million base pairs. 
     
     
         5 . The method of  claim 1 , wherein a cfDNA fragmentation profile is determined within each window. 
     
     
         6 . The method of  claim 1 , wherein cfDNA fragmentation profile comprises a median fragment size. 
     
     
         7 . The method of  claim 1 , wherein cfDNA fragmentation profile comprises a fragment size distribution. 
     
     
         8 . The method of  claim 1 , wherein the cfDNA fragmentation profile comprises a ratio of small cfDNA fragments to large cfDNA fragments in said windows of mapped sequences. 
     
     
         9 . The method of  claim 1 , wherein the cfDNA fragmentation profile comprises the sequence coverage of small cfDNA fragments in windows across the genome. 
     
     
         10 . The method of  claim 1 , wherein the cfDNA fragmentation profile comprises the sequence coverage of large cfDNA fragments in windows across the genome. 
     
     
         11 . The method of  claim 1 , wherein the cfDNA fragmentation profile comprises the sequence coverage of small and large cfDNA fragments in windows across the genome. 
     
     
         12 . The method of  claim 1 , wherein the cfDNA fragmentation profile is over the whole genome. 
     
     
         13 . The method of  claim 1 , wherein the cfDNA fragmentation profile is over a subgenomic interval. 
     
     
         14 . A method of identifying a mammal as having cancer, the method comprising:
 determining a cell free DNA (cfDNA) fragmentation profile in a sample obtained from the mammal;   comparing the cfDNA fragmentation profile to a reference cfDNA fragmentation profile; and   identifying the mammal as having cancer when the cfDNA fragmentation profile obtained from the mammal is different from the reference cfDNA fragmentation profile.   
     
     
         15 . The method of  claim 14 , wherein the reference cfDNA fragmentation profile is a cfDNA fragmentation profile of a healthy mammal. 
     
     
         16 . The method of  claim 15 , wherein the reference cfDNA fragmentation profile is generated by determining a cfDNA fragmentation profile in a sample obtained from the healthy mammal. 
     
     
         17 . The method of  claim 14 , wherein the reference DNA fragmentation pattern is a reference nucleosome cfDNA fragmentation profile. 
     
     
         18 . The method of  claim 14 , wherein the cfDNA fragmentation profile comprises a median fragment size, and wherein a median fragment size of the cfDNA fragmentation profile is shorter than a median fragment size of the reference cfDNA fragmentation profile. 
     
     
         19 . The method of  claim 14 , wherein the cfDNA fragmentation profile comprises a fragment size distribution, and wherein a fragment size distribution of the cfDNA fragmentation profile differs by at least 10 nucleotides as compared to a fragment size distribution of the reference cfDNA fragmentation profile. 
     
     
         20 . The method of  claim 14 , wherein the cfDNA fragmentation profile comprises a ratio of small cfDNA fragments to large cfDNA fragments in said windows of mapped sequences, wherein a small cfDNA fragment is 100 base pairs (bp) to 150 bp in length, wherein a large cfDNA fragments is 151 bp to 220 bp in length, and wherein a correlation of fragment ratios in the cfDNA fragmentation profile is lower than a correlation of fragment ratios of the reference cfDNA fragmentation profile. 
     
     
         21 - 67 . (canceled)