Yao Y.J.Ping X.L.Zhang H.Chen F.F.Lee P.K.Ahsan H.Chen C.-J.PO-HUANG LEEPeacocke M.Santella R.M.Tsou H.C.2020-11-192020-11-1919990950-9232https://www.scopus.com/inward/record.uri?eid=2-s2.0-0033587014&doi=10.1038%2fsj.onc.1202659&partnerID=40&md5=3bdac89ce9b803e057d61b5aa18e67c2https://scholars.lib.ntu.edu.tw/handle/123456789/521570Mutations 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]SDG3phosphatase; 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 Proteinsjournal article10.1038/sj.onc.1202659103403912-s2.0-0033587014