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Aberrant methylation of p14 ARF , p15 INK4b and p16 INK4a genes and location of the primary site in pulmonary squamous cell carcinoma
Author(s) -
Furonaka Osamu,
Takeshima Yukio,
Awaya Hirokazu,
Ishida Hajime,
Kohno Nobuoki,
Inai Kouki
Publication year - 2004
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2004.01663.x
Subject(s) - p14arf , pathology , basal cell , methylation , gene , cancer research , carcinoma , biology , medicine , tumor suppressor gene , genetics , carcinogenesis
Aberrant methylation of cytosines in CpG islands of the promoter regions of tumor suppressor genes is found in human tumors as a common mechanism of gene silencing. We investigated the methylation status of the chromosome 9p21 gene cluster ( p14 ARF , p15 INK4b and p16 INK4a genes) by methylation‐specific polymerase chain reaction in 20 central and 40 peripheral types of pulmonary squamous cell carcinoma (SqCC) in order to determine the differences between the pathogeneses of the central and peripheral types of SqCC. The frequencies of methylation were 30% for the p14 ARF gene, 20% for the p15 INK4b gene and 40% for the p16 INK4a gene in the central type and 25% for the p14 ARF gene, 10% for the p15 INK4b gene and 38% for the p16 INK4a gene in the peripheral type. Cases in which there was methylation of the p16 INK4a gene had a higher smoking index in the peripheral type ( P = 0.007). This trend was not detected in the central type. Methylation of two or three genes was observed in 55% of methylation in at least one gene of the central type but in only 17% of the peripheral type. This overlap methylation of the chromosome 9p21 gene cluster was found more frequently in the central type ( P = 0.02). These findings suggest one of the epigenetic differences between the central and peripheral types of SqCC.