Possible involvement of loss of heterozygosity in malignant transformation of ovarian endometriosis

Bing Xu, Xu B, Hamada S, Shinshichi Hamada, Kusuki I, Izumi Kusuki, Itoh R, Ryoji Itoh, Kitawaki J, Jo Kitawaki
Gynecologic Oncology · 2010 · vol. 120(2) , pp. 239–246 · doi:10.1016/j.ygyno.2010.10.036 · PMID:21130491 · W2039283711
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This paper investigated the potential role of loss of heterozygosity in the malignant transformation of ovarian endometriosis.

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Abstract

ObjectiveAlthough histological and epidemiological studies have suggested that endometriosis has malignant potential, the molecular mechanism underlying the malignant transformation of endometriosis is poorly understood. Ovarian cancer arising from endometriosis (OCEM) may provide an ideal model for genetic studies. To investigate the genetic alterations during transformation of ovarian endometriosis into cancer, we analysed loss of heterozygosity (LOH) and mutations of tumour-related genes in OCEM cases (n=12) that fulfilled the histological criteria and in solitary ovarian endometriosis (n=12).MethodsEach paraffin-embedded section was microdissected to isolate the endometriotic epithelium, transitional epithelium, and cancer cells. Extracted DNA was amplified by nested PCR. LOH was identified with fluorescence-labelled microsatellite markers. Mutations of tumour-related genes PTEN, TP53, and K-ras were examined by bidirectional DNA sequencing.ResultsWith 13 microsatellite markers on six chromosomes, we detected 31 and eight LOH events in OCEMs and in solitary ovarian endometriosis, respectively. In the OCEM group, 18 LOH events were found in cancer cells alone, while 13 LOH events were found in all cancer, transitional, and endometriotic tissues. High frequencies of LOH were detected on chromosomes 9p, 10q, and 13q. However, only two point mutations were detected in cancer cells in one case.ConclusionOur study suggested that accumulated LOH events on some chromosome loci may be involved in malignant transformation of endometriosis, while mutations in certain tumour-related genes are not.

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Condition tags

endometriosis

MeSH descriptors

Cell Transformation, Neoplastic Endometriosis Loss of Heterozygosity Ovarian Neoplasms Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adult Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Cell Transformation, Neoplastic Cell Transformation, Neoplastic Endometriosis Endometriosis Female Genes, p53 Genes, ras Genes, Tumor Suppressor Humans

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