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.

  • 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
PubMed ID
Appears In
Cancer Res, 2002, 62 (13)