Molecular genetic alterations in carcinoma ex-pleomorphic adenoma: A putative progression model?

To determine the genetic changes associated with the development of carcino ma ex-pleomorphic adenoma (Ca Ex-PA), we analyzed 15 microsatellite loci at chromosome arms 8q, 12q, and 17p on DNA from 26 neoplasms (including 8 mic rodissected benign and malignant components), and 13 pleomorphic adenomas f or comparison. Preomorphic adenomas and the adenoma component of Ca Ex-PAs showed a higher incidence of loss of heterozygosity (LOH) at chromosome arm s 8q (52%) and 12q (28%) than at 17p (14%) loci. in the carcinoma component , the combined LOH at chromosome arm 8q, 12q, and 17p regions was 69%, 50%, and 69%, respectively; within these chromosomal regions, 8q1 1.23-q12 (42% ), 12q23-qter (39%), 17p13 (41%), and 17p I I (45%) loci manifested the hig hest incidence of LOH. Eight carcinomas (30.7%) showed loss at all three ch romosomal arms tested. Of the eight microdissected Ca Ex-PAs analyzed, four adenoma and corresponding carcinoma components (50%) had the same LOH at 1 2q loci and additional LOH at 17p loci only in carcinomas. Chromosome arm 1 7p alterations correlated significantly with high disease stage and an incr eased proliferative rate In these tumors. Our results indicate that alterat ions at regions on chromosome arms 8q and/or 12q may constitute early event s associated with pleomorphic adenomas; that LOH at 12q loci may identify a subset of adenoma with potential progression to carcinoma; that acquisitio n of additional alterations at chromosome arm 17p loci might represent an e vent preceding malignant: transformation and progression; and that 8q, 12q, and 17p regions may harbor tumor suppressor genes involved in the genesis of PA and Ca Ex-PA. Genes Chromosomes Cancer 27:162-168, 2000, (C) 2000 Wil ey-Liss, Inc.