PTEN/MMAC1 mutations in hepatocellular carcinomas

Mutations in the PTEN/MMAC1 gene have been identified in several types of h uman cancers and cancer cell lines, including brain, endometrial, prostate, breast, thyroid, and melanoma. In this study, we screened a total of 96 he patocellular carcinoma (HCC) samples from Taiwan, where HCC is the leading cancer in males and third leading cancer in females, for mutations in the P TEN/MMAC1 gene. Complete sequence analysis of these samples demonstrated a missense mutation in exon 5 (K144I) and exon 7 (V255A) from HCC samples B6- 21 and B6-2, respectively. A putative splice site mutation was also detecte d in intron 3 from sample B6-2. Both B6-21 and B6-2 were previously shown t o contain missense mutations in the coding sequences of the p53 gene. Funct ional studies with the two missense mutations demonstrated that while mutat ion V255A in exon 7 resulted in a loss of phosphatase activity, mutation K1 44I in exon 5 retained its phosphatase activity. Additionally, we identifie d a silent mutation (P96P) in exon 5 of the PTEN/MMAC1 gene from HCC sample B6-22. These data provide the first evidence that the PTEN/MMAC1 gene is m utated in a subset of HCC samples.