Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas.
Abstract
We analyzed 921 adenocarcinomas of the esophagus, stomach, colon, and rectum to examine shared and distinguishing molecular characteristics of gastrointestinal tract adenocarcinomas (GIACs). Hypermutated tumors were distinct regardless of cancer type and comprised those enriched for insertions/deletions, representing microsatellite instability cases with epigenetic silencing of MLH1 in the context of CpG island methylator phenotype, plus tumors with elevated single-nucleotide variants associated with mutations in POLE. Tumors with chromosomal instability were diverse, with gastroesophageal adenocarcinomas harboring fragmented genomes associated with genomic doubling and distinct mutational signatures. We identified a group of tumors in the colon and rectum lacking hypermutation and aneuploidy termed genome stable and enriched in DNA hypermethylation and mutations in KRAS, SOX9, and PCBP1.
Authors
- Akbani R
- Bass AJ
- Bowlby R
- Bullman S
- Chatila W
- Cherniack AD
- Farshidfar F
- Hinoue T
- Islam M
- Kanchi RS
- Kim J
- Laird PW
- Lazar AJ
- Liu Y
- McCall SJ
- Mishra L
- Ojesina AI
- Pedamallu CS
- Rabkin CS
- Sakai R
- Sanchez-Vega F
- Schneider BG
- Seoane JA
- Sethi NS
- Thorsson V
- Wang KK
- Willis JE