Frameshift mutation at a mononucleotide repeat in CASP1 is rare in gastric and colorectal carcinomas with microsatellite instability

Abstract

Caspase-1 was initially identified as an activating enzyme for the proteolytic maturation of pro-interleukin-1β [ [1] Soung Y.H. Jeong E.G. Ahn C.H. Kim S.S. Song S.Y. Yoo N.J. et al. Mutational analysis of caspase 1, 4, and 5 genes in common human cancers. Hum Pathol. 2008; 39: 895-900 Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar ]. In addition, it is well known that caspase-1 overexpression induces apoptotic cell death. Evasion of apoptosis is one of the acquired capabilities of cancers and is considered a hallmark of cancer. Inactivation of apoptosis by somatic mutations of genes encoding proapoptotic proteins, including CASP8 and BAX, has been reported in human cancers [ 2 Kim H.S. Lee J.W. Soung Y.H. Park W.S. Kim S.Y. Nam S.W. et al. Inactivating mutations of caspase-8 gene in colorectal carcinomas. Gastroenterology. 2003; 125: 708-715 Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar , 3 Soung Y.H. Lee J.W. Kim S.Y. Jang J. Park Y.G. Park W.S. et al. CASPASE-8 gene is inactivated by somatic mutations in gastric carcinomas. Cancer Res. 2005; 65: 815-821 PubMed Google Scholar , 4 Mori Y. Sato F. Selaru F.M. Olaru A. Perry K. Kimos M.C. et al. Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers. Cancer Res. 2002; 62: 3641-3645 PubMed Google Scholar , 5 Mori Y. Yin J. Rashid A. Leggett B.A. Young J. Simms L. et al. Instabilotyping: comprehensive identification of frameshift mutations caused by coding region microsatellite instability. Cancer Res. 2001; 61: 6046-6049 PubMed Google Scholar ]. Frameshift mutations of genes containing mononucleotide repeats are features of colorectal and gastric cancers with microsatellite instability (MSI). There is a polyguanine (G8) in BAX gene that is frequently mutated in cancers with MSI [ 4 Mori Y. Sato F. Selaru F.M. Olaru A. Perry K. Kimos M.C. et al. Instabilotyping reveals unique mutational spectra in microsatellite-unstable gastric cancers. Cancer Res. 2002; 62: 3641-3645 PubMed Google Scholar , 5 Mori Y. Yin J. Rashid A. Leggett B.A. Young J. Simms L. et al. Instabilotyping: comprehensive identification of frameshift mutations caused by coding region microsatellite instability. Cancer Res. 2001; 61: 6046-6049 PubMed Google Scholar ]. The BAX mutant has a decreased apoptotic activity and is considered to contribute to cancer development.