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.