TY - JOUR
T1 - Comparative Molecular Analysis of Gastrointestinal Adenocarcinomas
AU - The Cancer Genome Atlas Research Network
AU - Liu, Yang
AU - Sethi, Nilay S.
AU - Hinoue, Toshinori
AU - Schneider, Barbara G.
AU - Cherniack, Andrew D.
AU - Sanchez-Vega, Francisco
AU - Seoane, Jose A.
AU - Farshidfar, Farshad
AU - Bowlby, Reanne
AU - Islam, Mirazul
AU - Kim, Jaegil
AU - Chatila, Walid
AU - Akbani, Rehan
AU - Kanchi, Rupa S.
AU - Rabkin, Charles S.
AU - Willis, Joseph E.
AU - Wang, Kenneth K.
AU - McCall, Shannon J.
AU - Mishra, Lopa
AU - Ojesina, Akinyemi I.
AU - Bullman, Susan
AU - Pedamallu, Chandra Sekhar
AU - Lazar, Alexander J.
AU - Sakai, Ryo
AU - Caesar-Johnson, Samantha J.
AU - Demchok, John A.
AU - Felau, Ina
AU - Kasapi, Melpomeni
AU - Ferguson, Martin L.
AU - Hutter, Carolyn M.
AU - Sofia, Heidi J.
AU - Tarnuzzer, Roy
AU - Wang, Zhining
AU - Yang, Liming
AU - Zenklusen, Jean C.
AU - Zhang, Jiashan (Julia)
AU - Chudamani, Sudha
AU - Liu, Jia
AU - Lolla, Laxmi
AU - Naresh, Rashi
AU - Pihl, Todd
AU - Wilkerson, Matthew D.
AU - Deyarmin, Brenda
AU - Hu, Hai
AU - Kvecher, Leonid
AU - Somiari, Stella
AU - Fantacone-Campbell, J. Leigh
AU - Hooke, Jeffrey A.
AU - Kovatich, Albert J.
AU - Shriver, Craig D.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/4/9
Y1 - 2018/4/9
N2 - 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. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1.
AB - 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. Liu et al. analyze 921 gastrointestinal (GI) tract adenocarcinomas and find that hypermutated tumors are enriched for insertions/deletions, upper GI tumors with chromosomal instability harbor fragmented genomes, and a group of genome-stable colorectal tumors are enriched in mutations in SOX9 and PCBP1.
KW - cancer
KW - colon
KW - colorectal
KW - epigenetic
KW - esophagus
KW - genomic
KW - methylation
KW - rectum
KW - stomach
KW - tumor
UR - http://www.scopus.com/inward/record.url?scp=85044904369&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2018.03.010
DO - 10.1016/j.ccell.2018.03.010
M3 - Article
C2 - 29622466
AN - SCOPUS:85044904369
SN - 1535-6108
VL - 33
SP - 721-735.e8
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -