Allelotyping defines minimal imbalance at chromosomal region 17q25 in non-serous epithelial ovarian cancers

Dion, F; Mes-Masson, Anne-Marie; Seymour, RJ; Provencher, Diane; Pn, Tonin

doi:10.1038/sj.onc.1203463

Cited by 21 publications

(53 citation statements)

References 40 publications

(71 reference statements)

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“…Tumour samples and peripheral blood lymphocytes were collected with informed consent from participants undergoing surgeries performed at the Research Centre of the University of Montreal Hospital Centre (CRCHUM)-Notre Dame Hospital site or from surgeries performed at the McGill University Health Centre -Montreal General Hospital as described (21,33). Clinical features such as disease stage, and tumour characteristics such as grade and histopathological subtype, were assigned by a gynecologiconcologist and/or gynecologic-pathologist according to the criteria established by the International Federation of Gynecology and Obstetrics as reported in previous studies for some cases (21,22,34) and summarized in Table I.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to these genes, DPH1 (17p13.3), HIC1 (17p13.3), NF1 (17q11.2), and RARA (17q21.1), have also been proposed to function as TSGs in EOC (11)(12)(13)(14). Unique loci exhibiting a high frequency of LOH have also been identified, suggesting the possibility of new TSGs in ovarian cancer (15)(16)(17)(18)(19)(20)(21)(22). It is thus likely that several genes act in concert in suppressing tumourigenicity and thus account for the unusually high frequency of LOH that often involves an entire chromosome 17 contig in ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

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Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer

et al. 2012

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Abstract. It has been proposed that the frequent loss of heterozygosity (LOH) of an entire chromosome 17 contig in epithelial ovarian cancers (EOC) is the consequence of the inactivation of multiple tumour suppressor genes on this chromosome. We report the characterization of a 453 Kb 17q25 locus shown previously to exhibit a high frequency of LOH in EOC samples. LOH analysis further defined the minimal region of deletion to a 65 Kb interval flanked by D17S2239 and D17S2244, which contains RHBDF2, CYGB and PRCD as tumour suppressor gene candidates. Tissue specific expression excluded PRCD as a candidate. RHBDF2 was expressed at low levels in the majority of benign and low malignant potential (LMP) tumours, and in a subset of malignant ovarian tumour samples, as compared with primary cultures of normal ovarian surface epithelial cell (NOSE) samples. CYGB was expressed at low levels in the majority of LMP and malignant samples compared with benign and NOSE samples. In contrast to CYGB expression, RHBDF2 was expressed at low or undetectable levels in EOC cell lines exhibiting tumourigenic characteristics and up-regulated in a genetically modified EOC cell line rendered non-tumourigenic. DNA sequence analysis identified variants but no apparent deleterious mutations in either gene. Methylation-specific PCR analysis suggested that promoter methylation of CYGB but not RHBDF2 occurred in 6 of 31 malignant samples. The results combined suggest that RHBDF2 and CYGB may play distinctive roles in ovarian cancer and could be added to the growing roster of chromosome 17 genes implicated in this disease.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chromosome 17q25 genes, RHBDF2 and CYGB, in ovarian cancer

et al. 2012

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“…Thus, p53 mutations may affect malignant transformation of endometriosis into EAC (16) 17q. The histologies of EOC displaying a pattern of 17q deletions were of the EAC, CCC and mucinous types (33). Tumor suppressor genes on 17q are possibly involved in development of endometriosis (2,34).…”

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

confidence: 99%

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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“…doi:10.1038 Keywords: ovarian cancer; cell lines; DNA microarray; chromosome 17; gene expression Epithelial ovarian cancer (EOC) is the second most common gynecological cancer and is responsible for almost half of deaths associated with gynecological pelvic malignancies. The molecular genetic analysis of EOC has revealed a significant role for chromosome 17 genes in the pathogenesis of ovarian malignancies through loss of heterozygosity (LOH) and karyotype studies (Eccles et al, 1990;Lee et al, 1990;Russell et al, 1990;Sato et al, 1991;Foulkes et al, 1993;Phillips et al, 1993;Tavassoli et al, 1993;Mertens et al, 1997;Dion et al, 2000). The frequent reduction to hemizygosity implies that numerous genes on both arms of chromosome 17 are implicated in EOC.…”

mentioning

confidence: 99%

“…A number of genes on the long arm of chromosome 17 also have been shown to be implicated in EOC: the ERBB2 oncogene at 17q21.1 (Slamon et al, 1989), the hereditary breast/ ovarian cancer TSG BRCA1 at 17q21.1 (Miki et al, 1994;Merajver et al, 1995) and the NME1 tumor metastasis marker gene at 17q21.3 (Mandai et al, 1994;Leary et al, 1995;Schneider et al, 1996Schneider et al, , 2000. In addition to the known genes implicated in ovarian tumorigenesis, LOH analysis and/or karyotype studies revealed the locations of novel TSGs on the long arm of chromosome 17 coincident with 17q21 (Tangir et al, 1996), 17q21-23 (Jacobs et al, 1993;Yang-Feng et al, 1993;Godwin et al, 1994), 17q23-qter (Mertens et al, 1997) and 17q25 (Kalikin et al, 1997, Dion et al, 2000. Other mechanisms not detected by these methods such as alterations in methylation patterns and alterations in promoter activity may be invoked, which alter the expression of genes.…”

mentioning

confidence: 99%