Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.
Microsatellite instability (MSI) within coding regions causes frameshift mutations (FSMs). This type of mutation may inactivate tumor suppressor genes in cancers with frequent MSI (MSI-H cancers). To identify novel FSMs in gastric carcinogenesis in an unbiased and comprehensive manner, we screened for this type of mutation at 154 coding region repeat loci in 18 MSI-H gastric cancers. We also compared FSM rates and spectra in MSI-H gastric versus colorectal cancers. Thirteen novel loci showed FSMs in >20% of gastric tumors. Novel loci with the highest mutation frequencies included the activin type 2 receptor gene (44.4%), DKFZp564K112 (a homologue of the Drosophila tumor suppressor gene multi-sex-combs; 41.2%), and an endoplasmic reticulum chaperone protein gene SEC63 (37.5%). The mutational spectra for genes with high mutation frequencies were also significantly different between MSI-H gastric and colorectal cancers.
Mori
Yuriko
Y
Department of Medicine, University of Maryland School of Medicine, Baltimore Veterans Affairs Hospital, Baltimore, Maryland 21201, USA.
Sato
Fumiaki
F
Selaru
Florin M
FM
Olaru
Andreea
A
Perry
Kellie
K
Kimos
Martha C
MC
Tamura
Gen
G
Matsubara
Nagahide
N
Wang
Suna
S
Xu
Yan
Y
Yin
Jing
J
Zou
Tong-Tong
TT
Leggett
Barbara
B
Young
Joanne
J
Nukiwa
Toshihiro
T
Stine
O Colin
OC
Abraham
John M
JM
Shibata
David
D
Meltzer
Stephen J
SJ
D015179:Colorectal Neoplasms / Q000235:genetics; D016368:Frameshift Mutation; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*