title: PTEN/MMAC1 mutations in hepatocellular carcinomas.
abstract: Mutations in the PTEN/MMAC1 gene have been identified in several types of human cancers and cancer cell lines, including brain, endometrial, prostate, breast, thyroid, and melanoma. In this study, we screened a total of 96 hepatocellular carcinoma (HCC) samples from Taiwan, where HCC is the leading cancer in males and third leading cancer in females, for mutations in the PTEN/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 detected in intron 3 from sample B6-2. Both B6-21 and B6-2 were previously shown to contain missense mutations in the coding sequences of the p53 gene. Functional studies with the two missense mutations demonstrated that while mutation V255A in exon 7 resulted in a loss of phosphatase activity, mutation K144I in exon 5 retained its phosphatase activity. Additionally, we identified 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 mutated in a subset of HCC samples.
authors.affiliation: Department of Dermatology, School of Public Health, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yao
authors.forename: X L
authors.initials: XL
authors.lastname: Ping
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: F F
authors.initials: FF
authors.lastname: Chen
authors.forename: P K
authors.initials: PK
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Ahsan
authors.forename: C J
authors.initials: CJ
authors.lastname: Chen
authors.forename: P H
authors.initials: PH
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Peacocke
authors.forename: R M
authors.initials: RM
authors.lastname: Santella
authors.forename: H C
authors.initials: HC
authors.lastname: Tsou
mesh_terms: D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins
chemical_list: D017931:DNA Primers; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human