Microsatellite instability and mutations of p53 and TGF-β RII genes in gastric cancer

Beatrice Renault, Daniele Calistri, Giovanni Buonsanti, Oriana Nanni, Dino Amadori, Guglielmina N. Ranzani

Research output: Contribution to journalArticle

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Abstract

To investigate the molecular mechanism of gastric carcinogenesis, we analyzed genetic instability and p53 gene mutations in 40 primary gastric carcinomas. Tumor samples were from untreated patients with no family history suggestive of genetic predisposition to cancer. We screened six microsatellite loci by the polymerase chain reaction (PCR) method, and exons 5-8 of the p53 gene by the PCR-based denaturing gradient gel electrophoresis and sequencing techniques. Microsatellite instability was detected in 32.5% (13/40), and gene mutations in 40% (16/40), of the tumors analyzed. No statistically significant associations were found between genetic alterations and clinico-pathological variables (with the exception of diffusion of lymph node metastases, which was inversely associated with the presence of microsatellite alterations; P <0.01). Interestingly, a negative association was found between genetic instability and p53 gene mutations: 11 out of 13 tumors showing instability proved to carry a nonmutated p53 gene versus 2/13 carrying a mutated gene (P = 0.03). These observations suggest that genetic instability and p53 gene mutations play a crucial role in the gastric carcinogenic process, but likely act through distinct pathways during cancer development. However, genetic instability is not in and of itself neoplastic. Therefore, we investigated whether insertion/deletion mutations of the polyadenine tract within the transforming growth factor-β type II receptor gene (TGF-β RII) were frequently present in gastric tumors with an RER+ (replication error) phenotype. We found RII mutations in 8/40 (20%) samples: mutations were present in 7/13 (54%) RER+ tumors versus 1/27 (4%) RER- cases (P <0.001).

Original languageEnglish
Pages (from-to)601-607
Number of pages7
JournalHuman Genetics
Volume98
Issue number5
Publication statusPublished - 1996

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Microsatellite Instability
Stomach Neoplasms
p53 Genes
Mutation
Stomach
Genes
Neoplasms
Microsatellite Repeats
INDEL Mutation
Polymerase Chain Reaction
Denaturing Gradient Gel Electrophoresis
Growth Factor Receptors
Transforming Growth Factors
Genetic Predisposition to Disease
Exons
Carcinogenesis
Lymph Nodes
Neoplasm Metastasis
Carcinoma

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Renault, B., Calistri, D., Buonsanti, G., Nanni, O., Amadori, D., & Ranzani, G. N. (1996). Microsatellite instability and mutations of p53 and TGF-β RII genes in gastric cancer. Human Genetics, 98(5), 601-607.

Microsatellite instability and mutations of p53 and TGF-β RII genes in gastric cancer. / Renault, Beatrice; Calistri, Daniele; Buonsanti, Giovanni; Nanni, Oriana; Amadori, Dino; Ranzani, Guglielmina N.

In: Human Genetics, Vol. 98, No. 5, 1996, p. 601-607.

Research output: Contribution to journalArticle

Renault, B, Calistri, D, Buonsanti, G, Nanni, O, Amadori, D & Ranzani, GN 1996, 'Microsatellite instability and mutations of p53 and TGF-β RII genes in gastric cancer', Human Genetics, vol. 98, no. 5, pp. 601-607.
Renault, Beatrice ; Calistri, Daniele ; Buonsanti, Giovanni ; Nanni, Oriana ; Amadori, Dino ; Ranzani, Guglielmina N. / Microsatellite instability and mutations of p53 and TGF-β RII genes in gastric cancer. In: Human Genetics. 1996 ; Vol. 98, No. 5. pp. 601-607.
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