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H‐ ras gene mutations in salivary gland mucoepidermoid carcinomas
Author(s) -
Yoo Jinyoung,
Robinson Robert A.
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000201)88:3<518::aid-cncr4>3.0.co;2-w
Subject(s) - mucoepidermoid carcinoma , transversion , carcinogenesis , point mutation , gene , mutation , salivary gland , cancer research , medicine , microbiology and biotechnology , biology , pathology , genetics
BACKGROUND The authors' recent investigation of salivary gland tumors in ras gene alteration has suggested that K ‐ ras activation may not play a role in their oncogenesis but H ‐ ras may, especially in mucoepidermoid carcinomas. A study was undertaken to assess the overall incidence of mutated H ‐ ras genes in mucoepidermoid carcinomas and to discover its potential correlation with clinicopathologic parameters. METHODS Fifty samples from patients with salivary gland mucoepidermoid carcinoma were analyzed for point mutations at codons 12, 13, and 61 of the H ‐ ras gene using the polymerase chain reaction followed by automated direct sequencing methodology. RESULTS Mutated H‐ ras genes were detected in 9 patients, for an overall incidence of 18% (9 of 50 patients). All but 1 of the mutations occurred at codon 12: a GGC‐to‐GTC transversion in 8 patients and a GGC‐to‐GAC transition in 1 patient, resulting in the amino acid substitution of valine and aspartic acid, respectively, for glycine. One of the samples showed concurrent mutations at codons 12 (GGC‐to‐GTC) and 13 (GGT‐to‐GGA). None of the samples demonstrated mutations involving codon 61. The H‐ ras mutations were observed in 5% (1of 21), 17% (2 of 12), and 35% (6 of 17) of low, intermediate, and high grade lesions, respectively. CONCLUSIONS These data suggest involvement of H‐ ras activation in conjunction with other yet‐unknown events in the development and/or progression of mucoepidermoid carcinomas. It is noteworthy that a stepwise increase in the frequency of H‐ ras mutations strongly correlates with tumor grade ( P = 0.017). Molecular analysis of this gene alteration may provide assistance in the determination of tumor grade and differentiation. Cancer 2000;88:518–23. © 2000 American Cancer Society.