somatic dna alterations in endometriosis high frequency of chromosome 17 and p53 loss in latestage endometriosis problem genetic predisposition to endometriosis is well established but the genes involved largely remain unknown although endometriosis is considered a benign disease it displays several features similar to malignancy altered morphology disregulated growth invasion we hypothesize endometriosis arises as result of somatic dna alterations occurring in a multistep process analogous to origin of neoplasia since chromosome 17 and tp53 tumor suppressor gene tsg alterations occur frequently in premalignant and malignant tissues including endometrial and ovarian epithelial carcinomas we sought to determine if similar somatic changes occur in late stage endometriosismethod of study to determine the frequencies of monosomy for chromosome 17 as well as for perturbations of p53 and other loci on 17 two different approaches were used fluorescent in situ hybridization fish analysis was used to detect monosomy for the 17 centromere and for the p53 locus for fish archival tissue n6 and fresh endometriotic touch preparations were prepared from women n8 undergoing extirpation of advanced stage endometriosis directlabeled probes specific for p53 17p131 and for the chromosome 17 alphasatellite centromere region 17111q111 were used to compare single glandular and stromal cells from endometriosis and normal tissue dna analysis of polymorphic dna loci were used to detect loss of heterozygosity loh for other loci on 17 we assessed matched endometriotic and normal dna peripheral blood from women with severelate stage disease n15 studying these dinucleotide markers hgh located on 17q2224 d17s250 17q112q12 and chrnb1 17p131results loss of the chromosome 17 centromere monosomy was shown by fish in some cells from all 14 endometriosis specimens although in no case did every cell show monosomy 17 in 12 of 14 specimens significant proportions of cells not only were monosomic for the chromosome 17centromere 8 to 42 of cells but also showed loss of p53 locus in the two remaining cases p53 loss alone was observed in 8 and 14 loh for other alleles on chromosome 17 was observed less often namely only 3 of 15 specimens for hgh 1 of 15 for d17s250 and 0 of 15 for chrnb1conclusions our study indicates that perturbations of chromosome 17 in general and the p53 locus in particular occur frequently in severelate stage endometriosis that not all cells show loss of whole chromosome 17 or the p53 locus suggests somatic mutation perhaps occurring late in the pathogenesis of endometriosis clonal evolution of endometriosis must depend not only on somatic mutations for p53 but also on other oncogenes or tsg alternatively the clone could begin with a germline or somatic mutation involving a nonneoplastic process followed by one or more somatic mutations involving an oncogene or tsg like p53 additional candidate genes clearly must be evaluated in order to determine the precise role chromosome 17 and p53 alterations play in endometriosis however additional genes seem unlikely to involve region connoted by hgh d17s250 or chrnb1