Loss of heterozygosity and microsatellite alterations in p53 and RB genes in adenoid cystic carcinoma of the salivary glands

Yuzo Yamamoto, Arvind K. Virmani, Ignacio I. Wistuba, Donald McIntire, Frank Vuitch, Jorge Albores-Saavedra, Adi F. Gazdar

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Adenoid cystic carcinomas (ACC) constitute approximately 20% of malignant salivary gland tumors. Several histological types of ACC are recognized and may coexist in a single tumor. The authors divided ACC into lower grade (tubular and cribriform subtypes) and higher grade (trabecular and solid) subtypes. A preliminary analysis of 10 ACCs showed a relatively high incidence of loss of heterozygosity (LOH) at the p53 and RB genes and low or absent K-ras mutations and LOH at chromosomal loci 3p, 5q, 8p, and 9p. From 21 tumors, the authors carefully microdissected and analyzed 36 subtype foci. Three interrelated pieces of evidence indicate that the relatively poor prognosis higher grade subtype arises from one or more of the lower grade subtypes via progression events associated with mutations in the p5 or RB genes. First, the number of mutations (both LOH and microsatellite alterations) at either gene is greater in higher grade foci than in lower grade foci; second, multiple mutations (two and occasionally three) are present in only higher grade foci; and third, when lower and higher grade loci are present in the same tumors, identical mutations plus other mutations are present in the corresponding higher grade foci. These findings suggest that molecular analyses of ACCs may provide information of prognostic importance.

Original languageEnglish (US)
Pages (from-to)1204-1210
Number of pages7
JournalHuman Pathology
Volume27
Issue number11
DOIs
StatePublished - Jan 1 1996

Keywords

  • adenoid cystic carcinoma
  • mutations
  • p53 gene
  • retinoblastoma gene
  • salivary gland

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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