title: Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.
abstract: 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.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore Veterans Affairs Hospital, Baltimore, Maryland 21201, USA.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Mori
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: Florin M
authors.initials: FM
authors.lastname: Selaru
authors.forename: Andreea
authors.initials: A
authors.lastname: Olaru
authors.forename: Kellie
authors.initials: K
authors.lastname: Perry
authors.forename: Martha C
authors.initials: MC
authors.lastname: Kimos
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.forename: Nagahide
authors.initials: N
authors.lastname: Matsubara
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Yin
authors.forename: Tong-Tong
authors.initials: TT
authors.lastname: Zou
authors.forename: Barbara
authors.initials: B
authors.lastname: Leggett
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.forename: O Colin
authors.initials: OC
authors.lastname: Stine
authors.forename: John M
authors.initials: JM
authors.lastname: Abraham
authors.forename: David
authors.initials: D
authors.lastname: Shibata
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics; D016368:Frameshift Mutation; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*