Frameshift mutations in TGFbetaRII, IGFIIR, BAX, hMSH3 and hMSH6 are absent in lung cancers.

A genome-wide instability at simple repeat sequences characterizes gastrointestinal and endometrial cancers of the microsatellite mutator phenotype (MMP). The genes encoding transforming growth factor-beta receptor type II (TGFbetaRII), insulin-like growth factor II receptor (IGFIIR), Bcl-2 associated X protein (BAX), hMSH3 and hMSH6 have simple repeat sequences in their coding regions. Consequently, mutations in the single repeat sequences in these genes provide one major route for carcinogenesis in these cancers. We examined 43 non-small cell lung carcinomas and 16 small cell carcinomas for frameshift mutations in simple repeat sequences of TGFbetaRII, IGFIIR, BAX, hMSH3 and hMSH6. In addition, MMP was assessed using a primer set for BAT-26. None of 59 lung cancers exhibited frameshift mutations or MMP. It is concluded that somatic frameshift mutations in these genes and MMP do not constitute important mechanisms in lung carcinogenesis. The possibility of some sort of genetic instability undetectable as a form of MMP cannot be precluded.