Mutations of the transforming growth factor β type II receptor gene and microsatellite instability in gastric cancer

✍ Scribed by Masayuki Ohue; Naohiro Tomita; Takushi Monden; Yasuo Miyoshi; Tadashi Ohnishi; Hikaru Izawa; Yuuichi Kawabata; Masaya Sasaki; Mitsugu Sekimoto; Isamu Nishisho; Hitoshi Shiozaki; Morito Monden

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 517 KB
• Volume: 68
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19961009)68:2<203::aid-ijc11>3.0.co;2-b

✦ Synopsis

Forty-three sporadic gastric cancers were analyzed with regard to whether mutations of simple repeated sequences in the transforming growth factor fi type II receptor ( T p -I / ) gene are associated with microsatellite instability (MSI) and gastric carcinogenesis. In 12 ofthe 43 cancers (28%), MSI was observed at least at I of the 2 microsatellite loci. Frameshift mutations of the TpR-/I gene, all of which were I base deletion of I0 adenine repeats, were detected in 3 of 6 cancers, with MSI at 2 loci. However, mutations were not detected in 6 cancers, with MSI only at I locus and 31 cancers without MSI. Moreover, microanalysis in these cases revealed that the mutant-type alleles of TpR-I/ were invariably common in different areas within the tumor. in contrast to the markedly variable alleles of microsatellite loci. Our results suggest that frameshift mutation of the T/3R-/I gene may be a critical event associated with MSI and may contribute to carcinogenesis of the stomach. One of the possible mechanisms of escape from growth control by TGFfi during gastric carcinogenesis could involve frameshift mutations of the TPR-II gene caused by DNA replication errors.