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胃癌におけるPTEN/MMAC1遺伝子変異：Dong-Yu WANG， 項芸岩，朱悦，田中正光，椙村春彦（浜松医大・一病理）

PTEN/MMAC1 mutations in gastric cancers: Dong-Yu WANG, Yun-Yan XIANG, Yue ZHU, Masamitsu TANAKA, Haruhiko SUGIMURA (1st Dept. Pathol. Hamamatsu Univ. Sch. Med.)

PTEN/MMAC1, a protein phosphatase, is a novel candidate tumor suppressor gene recently identified at 10q23. It is frequently mutated in brain, prostate and endometrial cancers but rare in lung, breast, kidney, thyroid cancers. It is also mutated in the germ line of patients with Cowden disease. To investigate whether mutation of PTEN/MMAC1 play an important role in gastroesophageal tumorigenesis, we examined 32 human gastric cancers and 12 human esophageal cancer cell lines by RT-PCR-SSCP and sequencing analysis in exon 5 to exon 8 of PTEN/MMAC1, in which the most mutations had been reported. SSCP variant bands were found in seven gastric cancers but not in any esophageal cancer cell lines. Sequence analysis confirmed that the mutations were presented in exon 5 of PTEN/MMAC1 in the seven gastric cancers. We noted that in the seven cases of mutated gastric cancers, four cases were also found the alteration in their corresponding noncancerous mucosa. These data indicate that PTEN/MMAC1 is inactivated in some gastric cancers and suggest that mutation of PTEN/MMAC1 is involved the carcinogenesis of human gastric cancers and may be an early event in this process.