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  • Original Paper
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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.

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Acknowledgements

The authors are grateful to Wang Qiao for assistance with DNA isolation. We also appreciate the technical assistance provided by the DNA Sequencing Core of the Skin Disease Research Center from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (PO-30 AR44535, to David R Bickers). This study is supported by the NCI (CA70519 to Monica Peacocke), the NIA (AG00760 to Hui C Tsou and AG00694 to Monica Peacocke) and NIEHS (ES05116 to Regina M Santella).

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Yao, Y., Ping, X., Zhang, H. et al. PTEN/MMAC1 mutations in hepatocellular carcinomas. Oncogene 18, 3181–3185 (1999). https://doi.org/10.1038/sj.onc.1202659

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