p53 mutations in gastric cancers from Taiwan

doi:10.1016/0304-3835(95)04077-3

Cancer Letters

Volume 100, Issues 1–2, 27 February 1996, Pages 107-113

https://doi.org/10.1016/0304-3835(95)04077-3 Get rights and content

Abstract

Mutations of the p53 gene were investigated in 80 surgical specimens of primary gastric cancer by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis. Mutations were detected in 18 tumors (22.5%) and localized to exons 5, 7 and 8. Mutations did not follow a random distribution among different subtypes, but instead clustered in the group of papillary adenocarcinomas, in which $712$ (58.3%) cases were mutated. Positivity for p53 mutation was significantly higher in intestinal-type (37.5%) than in diffuse-type carcinomas (12.5%). These results suggest that gene alterations of p53 are not rare and may participate in the carcinogenesis of intestinal-type carcinomas of the stomach. Twenty of 21 p53 mutations were represented by single nucleotide changes, mostly missense mutations (19 events) and one nonsense mutation. Transversional mutations constitute the majority of p53 mutations (65%) and only 20% of mutations show G:C to A:T transitions. It is possible that the etiologies of gastric cancer in different geographical areas are different.

References (23)

S.E. Goelz et al.
Purification of DNA from formaldehyde fixed and paraffin embedded human tissue
Biochem. Biophys. Res. Commun.
(1985)
L.L. Hsieh et al.
p53 gene mutations in brain tumors in Taiwan
Cancer Lett.
(1994)
T. Matozaki et al.
Missense mutations and a deletion of the p53 gene in human gastric cancer
Biochem. Biophys. Res. Commun.
(1992)
R. Seruca et al.
p53 alterations in gastric carcinoma: a study of 56 primary tumors and 204 nodal metastases
Cancer Gene Cytogen.
(1994)
G. Stemmermann et al.
The molecular biology of esophageal and gastric cancer and their precursors: oncogenes, tumor suppressor genes, and growth factors
Hum. Pathol.
(1994)
P. Correa et al.
Phenotypic and genotypic events in gastric carcinogenesis
Cancer Res.
(1994)
C.C. de Fromentel et al.
TP53 tumor suppressor gene, a model for investigating human mutagenesis
Gene Chromosome Cancer
(1992)
L. Dubeau et al.
Southern blot analysis of DNA extracted from formalin-fixed pathology specimens
Cancer Res.
(1986)
M. Fukunaga et al.
Im munohistochemical study of p53 in gastric carcinoma
Am. J. Clin. Pathol.
(1994)
M.S. Greenblatt et al.
Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis
Cancer Res.
(1994)

Health and Vital Statistics, Republic of China, 1992

(1993)

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p53 mutations in gastric cancers from Taiwan

Abstract

Biochem. Biophys. Res. Commun.

Cancer Lett.

Biochem. Biophys. Res. Commun.

Cancer Gene Cytogen.

Hum. Pathol.

Phenotypic and genotypic events in gastric carcinogenesis

Cancer Res.

TP53 tumor suppressor gene, a model for investigating human mutagenesis

Gene Chromosome Cancer

Southern blot analysis of DNA extracted from formalin-fixed pathology specimens

Cancer Res.

Im munohistochemical study of p53 in gastric carcinoma

Am. J. Clin. Pathol.

Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis

Cancer Res.

Health and Vital Statistics, Republic of China, 1992