Microsatellite DNA assays reveal an allelic imbalance in p16Ink4, GALT, p53, and APOA2 loci in patients with endometriosis

Goumenou, Anastasia G.; Arvanitis, Demetrios A.; Matalliotakis, Ioannis; Koumantakis, E.; Spandidos, Demetrios A.

doi:10.1016/s0015-0282(00)01663-0

Cited by 68 publications

(41 citation statements)

References 22 publications

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“…[23][24][25][26][27][28][29] Marker cM 2165T 2165E 914T 914E 247T 247E 18542T 18542E 11MT 11ME 10MT 10ME 8872T 8872E 842T 842E Chrm 3q D3S1614 169.9…”

Section: Discussionunclassified

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

Prowse

Manek

Varma

et al. 2006

Intl Journal of Cancer

146

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Histopathology and epidemiology studies have consistently demonstrated a strong link between endometriosis and endometriosisassociated ovarian cancers (EAOCs)-in particular, the endometrioid and clear cell subtypes. However, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link because similar factors predispose to both diseases. In order to search for evidence of clonal progression, we analyzed 10 EAOCs (endometrioid 5 4; clear cell 5 6) with coexisting endometriosis for common molecular genetic alterations in both the carcinoma and corresponding endometriosis. We used 82 microsatellite markers spanning the genome to examine loss of heterozygosity (LOH) in the coexisting carcinoma and endometriosis samples. A total of 63 LOH events were detected in the carcinoma samples; twenty two of these were also detected in the corresponding endometriosis samples. In each case, the same allele was lost in the endometriosis and cancer samples. Interestingly, no marker showed LOH in the endometriosis alone. These data provide evidence that endometriosis is a precursor to EAOCs. ' 2006 Wiley-Liss, Inc.

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“…[23][24][25][26][27][28][29] Marker cM 2165T 2165E 914T 914E 247T 247E 18542T 18542E 11MT 11ME 10MT 10ME 8872T 8872E 842T 842E Chrm 3q D3S1614 169.9…”

Section: Discussionunclassified

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

Prowse

Manek

Varma

et al. 2006

Intl Journal of Cancer

146

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“…By the time these implants or metaplastic lesions have developed into small endometriotic cysts, about one-third will harbor LOH (9,(11)(12)(13). LOH has commonly been identified in endometriosis at 1q, 5q, 6q, 9p, 10q, 11q, 17p, 22q (9,(11)(12)(13).…”

Section: Loh Analysismentioning

confidence: 99%

“…The genes for galactose-1-phosphate uridyl transferase (GALT) and apolipoprotein A2 (APOA2) have been mapped to chromosome 1q (11). Microsatellite DNA assays reveal an allelic imbalance in GALT and APOA2 loci in patients with endometriosis (11). SELENBP1 (selenium binding protein 1): location, 1q21-q22.…”

Section: Loh Involved In Clear Cell Carcinoma (Ccc) Of the Ovary: Thementioning

confidence: 99%

“…The CDKN2 (p16Ink4) gene, encoding the p16 protein, has been mapped to chromosome 9p21 (9,11,15). p16 is one of the cycle-dependent kinase inhibitors and acts as a negative cell-cycle regulator (21).…”

Section: Loh Involved In Clear Cell Carcinoma (Ccc) Of the Ovary: Thementioning

confidence: 99%

“…The 17p13 genetic locus is known to harbor the tumor suppressor gene p53 (11). The TP53 gene is the most frequently mutated gene in human cancers and plays a role as a transcription factor, causing cell cycle arrest or cell death.…”

Section: Loh Involved In Clear Cell Carcinoma (Ccc) Of the Ovary: Thementioning

confidence: 99%

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Molecular pathogenesis of endometriosis-associated clear cell carcinoma of the ovary (Review)

Kobayashi¹

2009

Oncol Rep

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Abstract. Epithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies. Among EOC, clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) differ from the other histological types with respect to their clinical characteristics and carcinogenesis. Both tumor types are often associated with endometriosis. EAC is recently reported to be characterized by K-RAS activation and PTEN dysfunction. However, the molecular changes in CCC remain largely unknown. The aim of this review is to summarize the current knowledge on the molecular mechanisms involved in CCC tumorigenesis. The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis-associated CCC of the ovary. Several recent studies of loss of heterozygosity (LOH), allelic loss, comparative genomic hybridization, mutation, methylation status, microarray gene-expression profiling and proteomics are discussed in the context of CCC biology. Retrograde menstruation or ovarian hemorrhage carries highly prooxidant factors, such as heme and iron, into the peritoneal cavity or ovarian endometrioma. A histologically normal ectopic endometrium bears genetic damages caused by irondependent oxidative stress. DNA damage or LOH caused by oxidative stress is a critical factor in the carcinogenic process. LOH studies have implicated the involvement of specific chromosomal regions (5q, 6q, 9p, 10q, 11q, 17q and 22q). Furthermore, the PTEN and APC (early event), p53, polo-like kinases, Emi1 and K-RAS (late event) genes may be involved in CCC carcinogenesis. The molecular pathology of CCC is heterogeneous and involves various putative precursor lesions and multiple pathways of development, possibly via genetic alteration by oxidative stress. the candidate tumor suppressor genes 7. Microsatellite instability in CCC 8. Genes specifically up-regulated in CCC 9. Clear cell adenofibroma-CCC sequence 10. Iron, oxidative stress and carcinogenesis 11. Conclusions IntroductionEpithelial ovarian cancer (EOC) is the leading cause of death in women with gynecological malignancies worldwide. The majority of patients present with stage III and IV disease, for which the 5-year survival rates are less than 20%. Most of the patients with EOC present with advanced disease that is not cured by surgery. Ninety per cent of EOC are derived from epithelium within inclusion cysts or from the ovarian surface epithelium and these neoplasms are classified into serous, mucinous, endometrioid adenocarcinoma (EAC), clear cell carcinoma (CCC) and other types (1).Molecular genetic alterations play a key role in carcinogenesis (1). High-grade serous carcinoma arises in a de novo fashion and is characterized by p53 mutations and BRCA1 and/or BRCA2 dysfunction. In contrast, low-grade serous carcinomas are characterized by activation of the RAS-RAF signaling pathway secondary to mutations in KRAS and BRAF in an adenoma-borderline tumor-carcinoma sequence. Similarly, mucinous carcinomas have also ...

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