PTEN/MMAC1 mutations in hepatocellular carcinomas
Journal
Oncogene
Journal Volume
18
Journal Issue
20
Pages
3181-3185
Date Issued
1999
Author(s)
Yao Y.J.
Ping X.L.
Zhang H.
Chen F.F.
Lee P.K.
Ahsan H.
Chen C.-J.
Peacocke M.
Santella R.M.
Tsou H.C.
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.
SDGs
Other Subjects
phosphatase; adult; aged; article; exon; human; human tissue; intron; liver cell carcinoma; major clinical study; missense mutation; priority journal; silent gene; Taiwan; tumor suppressor gene; Base Sequence; Carcinoma, Hepatocellular; DNA Primers; Female; Genes, Tumor Suppressor; Humans; Liver Neoplasms; Male; Middle Aged; Mutation; Phosphoric Monoester Hydrolases; PTEN Phosphohydrolase; Tumor Suppressor Proteins
Type
journal article