J Gastric Cancer.  2010 Sep;10(3):91-98.

Genetic and Expression Analysis of the SIRT1 Gene in Gastric Cancers

• Cao Z
• Song JH
• Kang YW
• Yoon JH
• Nam SW
• Lee JY
• Park WS

Abstract

PURPOSE
Silent mating-type information regulation 2 homologue 1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. SIRT1 plays an important role in the regulation of cell death/survival and stress response in mammals. The aim of this study was to investigate whether the SIRT1 gene is involved in the development or progression of gastric cancers.
MATERIALS AND METHODS
SIRT1 and p53 genes in 86 gastric cancers were examined for genetic alterations by PCR-single strand conformation polymorphism sequencing, as well as SIRT1 protein expression in 170 gastric cancers by immunohistochemistry.
RESULTS
In the genetic analysis, we found SIRT1 and p53 mutations in two and 12 cases, respectively. Two missense mutations, c.599 C>T (T200I) and c.1258 G>A (E420K), were detected in the SIRT1 gene coding region. The SIRT1 and p53 mutation were found in mutually exclusive gastric cancers. The immunohistochemistry revealed that SIRT1 overexpression was found in 95 (55.9%) of 170 gastric cancers. Altered SIRT1 expression was not statistically associated with clinicopathological parameters, including tumor differentiation, location, lymph node metastasis, or p53 expression. Two cases with an SIRT1 mutation showed increased SIRT1 expression.
CONCLUSIONS
These results suggest that genetic alterations and overexpression of the SIRT1 gene may contribute to gastric cancer development.

Keyword

Gastric cancer; SIRT1; p53; Mutation; Immunohistochemistry

MeSH Terms

Adenine
Clinical Coding
Genes, p53
Immunohistochemistry
Lymph Nodes
Mammals
Mutation, Missense
Neoplasm Metastasis
Niacinamide
Stomach Neoplasms
Adenine
Niacinamide

Figure

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  Fig. 1 Aberrant SIRT1 expression in gastric cancer cells. Normal gastric mucosa exhibited focal weak positive staining for SIRT1 (A). Intestinal-(B) and diff use-type (C) gastric cancers displayed nuclear staining for SIRT1 (Original magnification, ×200).

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  Fig. 2 Representative mutations of the SIRT1 gene (A & B) and p53 gene (C & D) detected in gastric cancer. SSCP demonstrating aberrant bands (arrow) and sequencing data showing missense mutations: (A) c.599 C>T (T200I), (B) c.1258 G>A (E420K) in the SIRT1 gene, (C) c.488A>G (Y163C), (D) c.440T>G (V147G) in the p53 gene (N = non-neoplastic DNA; T = tumor DNA).

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