Comparative genomic hybridization and loss of heterozygosity analyses identify a common region of deletion at 15q11.1-15 in human malignant mesothelioma

Comparative genomic hybridization analysis Bas performed to identify chromo somal imbalances in 24 human malignant mesothelioma (MM) cell lines derived from untreated primary tumors. Chromosomal losses accounted for the majori ty of genomic imbalances. The most frequent underrepresented segments were 22q (58%) and 15q11.1-21 (54%); other recurrent sites of chromosomal loss i ncluded 1p12-22 (42%), 13q12-14 (42%), 14q23-qter (42%), 6q25-qter (38%), a nd 9p21 (38%). The most commonly overrepresented segment was 5p (54%). DNA sequence amplification at 3p12-13 was observed in two cases, Whereas some o f the regions of copy number decreases (i.e., segments in Ip, 6q, 9p, and 2 2q) have previously been shown to be common sites of karyotypic and allelic loss in MM, our comparative genomic hybridization analyses identified a ne w recurrent site of chromosomal loss,within 15q in this malignancy. To more precisely map the region of 15q deletion, loss of heterozygosity analyses were performed with a panel of polymorphic microsatellite markers distribut ed along 15q, which defined a minimal region of chromosomal lass at 15q11.1 -15. The identification of frequent losses of a discrete segment in 15q sug gests that this region harbors a putative tumor suppressor gene whose loss/ inactivation may contribute to the pathogenesis of many MMs.