Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers.
Abstact
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
- Abraham JM
- Kimos MC
- Leggett B
- Matsubara N
- Meltzer SJ
- Mori Y
- Nukiwa T
- Olaru A
- Perry K
- Sato F
- Selaru FM
- Shibata D
- Stine OC
- Tamura G
- Wang S
- Xu Y
- Yin J
- Young J
- Zou TT