Potential Role of the Inactivated X Chromosome in Ovarian Epithelial Tumor Development

Cheng, Pui C.; Gosewehr, Jim A.; Kim, Timothy M.; Velicescu, Mihaela; Wan, Minghong; Zheng, Jianping; Felix, Juan C.; Cofer, Kenneth F.; Luo, Ping; Biela, Barbara H.; Godorov, Gary; Dubeau, Louis

doi:10.1093/jnci/88.8.510

Cited by 73 publications

(55 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This conclusion is also supported by recent data from our laboratory (Cheng et al, 1996). The available evidence therefore supports the notion that LMP tumours are mechanistically more complex than cystadenomas and strongly argues in favour of maintaining the distinction between these two variants of ovarian epithelial tumours, in spite of the fact that they often show similar clinical behaviour.…”

Section: Discussionsupporting

confidence: 86%

“…Although such changes are clearly associated with the malignant phenotype in a large number of different tumour types (Gama-Sosa et al, 1983), they are also found in some benign neoplasms such as colorectal polyps (Goelz et al, 1985;Feinberg et al, 1988). Ovarian epithelial tumours are a good model to address this question because there are two well-defined subtypes of these tumours that do not fully express the malignant phenotype (Cheng et al, 1996) and can therefore be regarded as different early stages of malignant transformation. The results of our experiments clearly show that DNA methylation changes are present in both, ovarian LMP tumours and carcinomas, lending further support to the idea advanced by Goelz et al (1985) that such changes are early events in malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

Cheng

Schmütte²,

Cofer³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary We compared global levels of DNA methylation as well as methylation of a specific locus (MyoDl) in ovarian cystadenomas, ovarian tumours of low malignant potential (LMP) and ovarian carcinomas to investigate the association between changes in DNA methylation and ovarian tumour development. As we realized that cystadenomas showed different methylation patterns from both LMP tumours and carcinomas, we verified their monoclonal origin as a means of confirming their true neoplastic nature. High-pressure liquid chromatographic (HPLC) analyses showed that global methylation levels in LMP tumours and carcinomas were 21% and 25% lower than in cystadenomas respectively (P = 0.0001 by one-way variance analysis). Changes in the methylation status of the MyoDl locus were not seen in any of ten cystadenomas analysed but were present in five of ten LMP tumours and in five of ten carcinomas (P = 0.03). These findings suggest that alterations in DNA methylation are absent (or at least not as extensive) in ovarian cystadenomas, but are present in LMP tumours, the phenotypic features of which are intermediate between those of benign and malignant ovarian tumours. The results also emphasize the merit of distinguishing ovarian LMP tumours from cystadenomas, in spite of their similar clinical characteristics.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

Cheng

Schmütte²,

Cofer³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…19 The LOH frequency on Xq has been reported to be 50% and that on all other chromosomes is less than 10% in LMP. 20 In the present study, LOH of the AR locus was observed in 50% of serous OC cases but was not found in other types of ovarian tumors. Moreover, mucinous LMP accounted for 84% of our cases, whereas 26% of cases were mucinous LMP in the study of Cheng et al 20 This discrepancy in LOH frequency may be attributed to the different incidence of each histologic subtype.…”

Section: Loh Analysis In Ovarian Tissues From Different Lesionscontrasting

confidence: 54%

Comprehensive allelotype study of ovarian tumors of low malignant potential: Potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma

Nakayama

Takebayashi

Namiki³

et al. 2001

Int. J. Cancer

View full text Add to dashboard Cite

Ovarian tumors of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas (OC); however, the relevance of LMP to ovarian carcinogenesis is not clear. We performed a comparative analysis of allelotypes in 50 cases of LMP (42 mucinous and 8 serous) and 23 cases of OC (15 mucinous and 8 serous) to investigate any differences in genetic changes. Analysis of loss of heterozygosity (LOH) using 25 microsatellite markers reportedly associated with OC revealed that the total LOH frequency at each marker was significantly lower in LMP than in OC (p < 0.01). However, 9 (36%) loci showed higher LOH frequency in mucinous LMP than in mucinous OC. A genome-wide scan for LOH using 91 microsatellite markers and fine mapping revealed that LOH at D7S1805 (7q35) is characteristic of mucinous LMP (19.4% in mucinous LMP, 8.3% in mucinous OC). We further studied LOH in 3 cases of mucinous OC that were accompanied by mucinous LMP lesions. In 2 cases, LOH frequency was higher in the carcinoma portion than in the morphologically LMP portion. The other case showed microsatellite instability in the morphologically LMP portion and LOH in the carcinoma portion. Our results suggest the presence of an LMP-to-OC developmental sequence and the existence of a subset of LMP that does not develop into OC in the mucinous subtype of ovarian tumors. © 2001 Wiley-Liss, Inc. Key words: ovarian carcinogenesis; genome; mucinous LMP; serous LMP; loss of heterozygosity (LOH)Among gynecologic malignancies, ovarian carcinoma (OC) is the leading cause of death. 1,2 Ovarian tumors of low malignant potential (LMP) are a distinctive subtype of ovarian epithelial tumor characterized as an intermediate stage between clearly benign and OC. One of the histologic criteria of LMP or borderline malignancy is atypical epithelial proliferation without ovarian stromal invasion. It remains to be determined whether LMP is a precursor of OC or a unique type of tumor that will not progress to OC.It is well established that carcinogenesis of solid tumors requires a series of genetic changes involving activation of oncogenes and inactivation of tumor suppressor genes. In OC, mutational activation of the K-ras gene, inactivation of the p53 gene and overexpression/amplification of the erb-B2 gene have been reported. [3][4][5] Mutations and loss of heterozygosity (LOH) of the p53 tumor suppressor gene on chromosome 17p13.1 are rare events in LMP. 6 LOH of chromosomes 7p, 7q, 9q and 11q has been reported to be involved in the early stages of ovarian carcinogenesis. 7 The incidence of K-ras mutations is higher in OC than in LMP, especially in the mucinous subtype. 8 These findings suggest that LMP may represent a pathologic continuum between benign tumors and OC. However, the molecular genetic changes in LMP are not well understood compared with OC, as only a few instances have been analyzed of LOH occurring in a small number of cases of LMP. 8 -11 To elucidate the biological relevance of LMP to ovarian carcinogenesis, we compared allelotypes between...

show abstract

“…Critical to this examination is the role that tumor suppressor genes play in the development of ovarian cancer. Cytogenetic and molecular studies have attempted to pinpoint the sites of alteration leading to the development of this disease by noting alterations at chromosome 3p (Tanaka et al, 1989), 5q (Weitzel et al, 1994), 6q (Rodabaugh et al, 1995b;Lee et al, 1990;Foulkes et al, 1993b;Sato et al, 1991), 9p (Rodabaugh et al, 1995a), 11 (Eccles et al, 1992a;Davis et al, 1996;Lee et al, 1990;Gallion et al, 1990Gallion et al, , 1992, 13 (Yang-Feng et al, 1992Sato et al, 1991;Gallion et al, 1992;Dodson et al, 1993), 17 (Wertheim et al, 1994;Foulkes et al, 1993a;Eccles et al, 1992b;Tangir et al, 1996;Pieretti et al, 1995;Lee et al, 1990;Cliby et al, 1993;Yang-Feng et al, 1993;Gallion et al, 1992;Dodson et al, 1993), 19 (Sato et al, 1991), 22 (Bryan et al, 1996), and X (Yang-Feng et al, 1992;Cheng et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Identification of a 1300 kilobase deletion unit on chromosome 7q31.3 in invasive epithelial ovarian carcinomas

et al. 1997

View full text Add to dashboard Cite

Potential Role of the Inactivated X Chromosome in Ovarian Epithelial Tumor Development

Cited by 73 publications

References 0 publications

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis

Comprehensive allelotype study of ovarian tumors of low malignant potential: Potential differences in pathways between tumors with and without genetic predisposition to invasive carcinoma

Identification of a 1300 kilobase deletion unit on chromosome 7q31.3 in invasive epithelial ovarian carcinomas

Contact Info

Product

Resources

About