Journal
NATURE GENETICS
Volume 47, Issue 9, Pages 1047-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3343
Keywords
-
Categories
Funding
- US National Institutes of Health [T32 HL007627]
- Dana-Farber/Harvard Gastrointestinal Cancer Specialized Programs of Research Excellence [P50CA127003]
- National Human Genome Research Institute (NHGRI) Large-Scale Sequencing Program [U54 HG0003067]
- National Cancer Institute [U54 CA163059, P01 CA098101, U54 CA163004]
- Broad Institute SPARC
- American Cancer Society
Ask authors/readers for more resources
Barrett's esophagus is thought to progress to esophageal adenocarcinoma (EAC) through a stepwise progression with loss of CDKN2A followed by TP53 inactivation and aneuploidy. Here we present whole-exome sequencing from 25 pairs of EAC and Barrett's esophagus and from 5 patients whose Barrett's esophagus and tumor were extensively sampled. Our analysis showed that oncogene amplification typically occurred as a late event and that TP53 mutations often occurred early in Barrett's esophagus progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data showed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations, with more frequent oncogenic amplification and less frequent inactivation of tumor suppressors, including CDKN2A. These data suggest that many EACs emerge not through the gradual accumulation of tumor-suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by the acquisition of oncogenic amplifications.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available