Detection of chromosomal aneuploidy in endometriosis by multi-color fluorescence in situ hybridization (FISH)

Abstract

Endometriosis affects 10-15% of women of reproductive age and is a common cause of infertility and pelvic pain. Although endometriosis is characterized by abnormal growth or turn-over of cells, the genetic changes involved remain unclear. We employed a multi-color fluorescence in situ hybridization (FISH) strategy to determine the incidence of somatic chromosomal numeric alterations in severe/late stage endometriosis. Using alpha-satellite sequence-specific DNA probes for chromosomes 7, 8, 11, 12, 16, 17, and 18, simultaneous two- and three-color FISH were performed to evaluate the frequency of monosomic, disomic, and trisomic cells in normal control and endometriotic tissue specimens. In one of four endometriosis samples studied, a significantly higher frequency of monosomy for chromosome 17 (14.8%, chi 2(4) = 53.3, P < 0.0001) and 16 (8.8%, chi 2(4) = 11.4, P < 0.05) was observed. An increased number of cells with chromosome 11 trisomy (14.8%, chi 2(4) = 96.2, P < 0.0001) were detected in a second case. In a third case, a distinct colony of nuclei with chromosome 16 monosomy (14.1%, chi 2(4) = 21.39, P < 0.005) was detected. Acquired chromosome-specific aneuploidy may be involved in endometriosis, reflecting clonal expansion of chromosomally abnormal cells. That candidate tumor suppressor genes and oncogenes have been mapped to chromosomes 11, 16, and 17 suggests that chromosomal loss or gain plays a role in the development and/or progression of endometriosis.

Detection of DNA copy number changes in human endometriosis by comparative genomic hybridization

“…However, recent molecular allelotyping work has detected somatic genetic changes, expressed as loss of heterozygosity (LOH) distributed along several chromosomes in 11 of 40 (28%) endometriotic samples (Jiang et al 1998). Moreover, clonal expansion of abnormal cells with monosomies 16 and 17 and trisomy of chromosome 11 was reported in ovarian endometriomas using the FISH strategy (Shin et al 1997).…”

Ovarian cancer in endometriosis: molecular biology, pathology, and clinical management

“…The most widely accepted candidate for the origin of ovarian cancer is the so-called ovarian surface epithelium (OSE), a single layer of fl attened cells covering the ovarian surface. Pathological fi ndings have shown that OSE can be endowed tion, or microsatellite analysis have revealed genomic abnormalities, such as loss of heterozygosity (LOH) of chromosomes 1p, 9p, 11q, 17p, and 22q, and amplifi cation of 17q, [16][17][18][19] again indicating the clonal evolution of this disease. Sato et al 20 reported somatic mutation of PTEN in solitary endometriosis.…”

Genetic influences on endometriosis in an Australian twin sample

“…Other evidence of a genetic basis for endometriosis comes from nonhuman primates (26). Molecular and cytologic research has suggested a possible path for genetic control of endometriosis (27,28). Several candidate genes have been identified for investigation, including genes involved in galactose metabolism and dioxin detoxification (22).…”