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Mutations of the tumour suppressor gene p53 in colorectal and hepatocellular carcinomas.
Shi, C Y; Phang, T W; Wee, A; Ngoi, S S; Lin, Y; Li, B; Ong, C N; Lee, H P.
Afiliação
  • Shi CY; Department of Community, Occupational and Family Medicine, National University of Singapore.
Ann Acad Med Singap ; 24(2): 204-10, 1995 Mar.
Article em En | MEDLINE | ID: mdl-7653961
The present study describes mutations of the tumour suppressor gene p53 in a local collection of colorectal and hepatocellular carcinomas (HCCs). Tumour DNA was extracted from both fresh and paraffin-embedded tissues and exons 5-8 of the p53 gene were amplified by polymerase chain reaction (PCR). Mutations were detected by single-strand conformation polymorphism (SSCP) analysis followed by direct DNA sequencing. Of the 38 colorectal carcinomas and 42 HCCs examined, 15 (39%) and 13 (31%), respectively, showed p53 mutations. Two-thirds (10/15) of the mutations in colorectal carcinomas were base transitions with a predominance at CpG dinucleotide sites--a pattern characteristic to an endogenous process in cancer development. Three mutational hotspots at codons 175, 248 and 282 were also identified. Mutations did not correlate with histological grade, Dukes stage, or metastasis. However, tumours at the distal site of the colorectum showed a higher proportion of mutations than the proximal site. In the case of HCCs, majority (9/13) of the mutations were base transitions and no mutations were observed at codon 249. This is in contrast to results from other high-incidence areas such as Africa and China, where aflatoxin is believed to be a major aetiologic factor for liver cancers. The results therefore suggest that other risk factors, rather than dietary exposure to aflatoxin, may contribute to the high HCC incidence in Singapore.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenocarcinoma / Biomarcadores Tumorais / Genes p53 / Carcinoma Hepatocelular / Neoplasias Hepáticas / Mutação Tipo de estudo: Incidence_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País/Região como assunto: Asia Idioma: En Revista: Ann Acad Med Singap Ano de publicação: 1995 Tipo de documento: Article País de publicação: Singapura
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Adenocarcinoma / Biomarcadores Tumorais / Genes p53 / Carcinoma Hepatocelular / Neoplasias Hepáticas / Mutação Tipo de estudo: Incidence_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País/Região como assunto: Asia Idioma: En Revista: Ann Acad Med Singap Ano de publicação: 1995 Tipo de documento: Article País de publicação: Singapura