Cell-free DNA for assessing and/or treating cancer
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 treating a subject comprising:
identifying a subject as having cancer by determining a cell free DNA (cfDNA) fragmentation profile of sequenced fragments in a sample obtained from the subject, wherein the sequenced fragments are obtained through whole genome sequencing (WGS);
mapping the sequenced fragments to a genome to obtain windows of mapped sequences;
analyzing the windows of mapped sequences to determine the cfDNA fragmentation profile;
analyzing the cfDNA fragmentation profile against a reference cfDNA fragmentation profile from a healthy subject; wherein the cfDNA fragmentation profile comprises a ratio of small cfDNA fragments to large cfDNA fragments;
detecting that the cfDNA fragmentation profile obtained from the subject is more variable than the reference cfDNA fragmentation profile, wherein increased variability of the fragmentation profile obtained from the subject is indicative of the subject as having cancer; and
administering to the subject identified as having cancer, an immunotherapeutic treatment suitable for the treatment of cancer, thereby treating the subject.
2. The method of claim 1 , 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.
3. The method of claim 1 , wherein the immunotherapeutic treatment is a treatment selected from the group consisting of immunotherapy, adoptive T cell therapy, targeted therapy, and combinations thereof.
4. The method of claim 1 , wherein the reference cfDNA fragmentation profile is generated by determining a cfDNA fragmentation profile in a sample obtained from the healthy subject.
5. The method of claim 1 , wherein the reference DNA fragmentation pattern is a reference nucleosome cfDNA fragmentation profile.
6. The method of claim 1 , wherein determining of the cfDNA fragmentation profile comprises determining 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.
7. The method of claim 1 , wherein determining of the cfDNA fragmentation profile comprises determining 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.
8. The method of claim 1 , wherein the cfDNA fragmentation profile comprises a ratio of small cfDNA fragments to large cfDNA fragments in windows of mapped sequences, wherein a small cfDNA fragment is about 100 base pairs (bp) to 150 bp in length, wherein a large cfDNA fragment is about 151 bp to 220 bp in length.
9. The method of claim 1 , wherein the cfDNA fragmentation profile comprises small cfDNA fragments in windows across the genome.
10. The method of claim 1 , wherein the cfDNA fragmentation profile comprises large cfDNA fragments in windows across the genome.
11. The method of claim 1 , wherein the cfDNA fragmentation profile comprises small and large cfDNA fragments in windows across the genome.
12. The method of claim 1 , wherein analyzing the cfDNA fragmentation profile against a reference cfDNA fragmentation profile from a healthy subject comprises analyzing the cfDNA fragmentation profile relative to a reference cfDNA fragmentation profile over a subgenomic interval.
13. The method of claim 8 , wherein genome coverage of the mapped sequences is from about 2×, 1×, 0.5×, 0.2× or 0.1×.
14. The method of claim 1 , wherein each window is from thousands to millions of bases in length.
15. The method of claim 8 , wherein the correlation of small to large fragment ratios in the cfDNA fragmentation profile for a subject with cancer as compared to the reference cfDNA fragmentation profile is lower than a correlation of small to large fragment ratios for a healthy subject as compared to the reference cfDNA fragmentation profile.
16. The method of claim 1 , wherein the sample is selected from the group consisting of blood, serum, plasma, amnion, tissue, urine, cerebrospinal fluid, saliva, sputum, broncho-alveolar lavage, bile, lymphatic fluid, cyst fluid, stool, ascites, pap smears, breast milk, and exhaled breath condensate.
17. The method of claim 1 , further comprising administering to the subject a treatment including surgery, chemotherapy, radiation therapy, hormone therapy, cytotoxic therapy or a combination thereof.
18. The method of claim 1 , wherein a cell free DNA (cfDNA) fragmentation profile is also determined during and/or after administration of the treatment.