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.
Gotoh
K
K
Department of Internal Medicine and Pulmonary Medicine, Aichi Cancer Center Hospital, Nagoya University School of Medicine, Japan.
Yatabe
Y
Y
Sugiura
T
T
Takagi
K
K
Ogawa
M
M
Takahashi
T
T
Mitsudomi
T
T
D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D017451:Receptors, Somatomedin / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D051028:bcl-2-Associated X Protein
D017931:DNA Primers; D004268:DNA-Binding Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000074081:MutS Homolog 3 Protein; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D017451:Receptors, Somatomedin; D018125:Receptors, Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C094443:G-T mismatch-binding protein; C078444:MSH3 protein, human; C421109:multidrug resistance-associated protein 1