Overexpression of WDR62 is associated with centrosome amplification in human ovarian cancer

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Abstract

Purpose

To assess the clinical significance of WD40 repeat containing 62 (WDR62), a novel centrosome abnormalities-associated gene, in ovarian cancer.

Materials and methods

In this study, WDR62 expression was assessed by western blot (6 ovarian cancer cell lines) and immunohistochemistry (primary epithelial ovarian cancer clinical specimens), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence staining in ovarian cancer cell lines, and by immunohistochemistry staining in ovarian cancer samples.

Results

Six ovarian cancer cell lines exhibited significant WDR62 protein overexpression, and amplification of centrosome. High-grade ovarian cancer specimens exhibited significantly stronger nuclear staining of WDR62 than low-grade ovarian carcinoma specimens (80.4% vs 41.3%; P<0.012). High WDR62 expression was strongly associated with supernumerary centrosome count in tumor cells ( P < 0.001).

Conclusion

Our findings suggest that WDR62 overexpression is related to centrosome amplification in ovarian cancer. It may be a novel useful differentiation biomarker and a potential therapy target for OC. Further assessment of WDR62 expression is highly warranted in large, prospective studies.

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Most cited references 17

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Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy.

I Sato, Y. Kikuchi, T Kamura … (2000)

A retrospective review of treatment results comparing women with clear cell carcinoma of the ovary (CCC) with a group with serous adenocarcinoma of the ovary (SAC) was conducted. Between 1988-1998, 662 patients with epithelial ovarian carcinoma were identified through the medical records department and the tumor registry at 4 institutions. After the central pathologic review, 101 patients with pure or dominant (>/= 90%) CCC (15.3%) were entered into the current study. Two hundred thirty five patients with pure SAC were selected as a group for comparison. All patients underwent staging laparotomy followed by platinum-based chemotherapy. Distribution of the International Federation of Gynecology and Obstetrics (FIGO) disease stage, response to chemotherapy, and prognosis for patients with CCC were compared with the same values in patients with SAC. Patients with CCC were significantly more likely to have FIGO Stage I disease than were patients with SAC (48.5% vs. 16.6%). A high recurrence rate was noted in those patients with Stage IC CCC (37%). In those patients with Stage IC disease, the survival rates for patients with CCC were lower than those for patients with SAC. The 3-year and 5-year survival rates for Stage III CCC patients were significantly lower compared with Stage III SAC patients. The response rate to platinum-based chemotherapy in patients with CCC was significantly lower than that in patients with SAC. CCC is an intriguing histologic type of epithelial ovarian cancer that demonstrates a clinical behavior distinctly different from that of SAC. Copyright 2000 American Cancer Society.

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Whole exome sequencing identifies recessive WDR62 mutations in severe brain malformations

Kaya Bilgüvar, Ali Öztürk, Angeliki Louvi … (2010)

The development of the human cerebral cortex is an orchestrated process involving the birth of neural progenitors in the peri-ventricular germinal zones, cell proliferation characterized by both symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in 6 highly ordered, functionally-specialized layers 1,2 . An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development (MCD) 3-6 . Mapping of disease loci in putative Mendelian forms of MCD has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WDR62 as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with WDR62 mutations had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mouse and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. WDR62 expression in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the utility of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.

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The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin.

Robert Kurman, C R Boice, Moutaz Haiba … (2003)

Advances over the past decade suggest a need to reassess the distribution of ovarian surface epithelial tumors. A series of 220 consecutive invasive ovarian carcinomas, including carcinosarcomas and peritoneal carcinomas, was reviewed. Notable findings include: 7% of tumors were carcinosarcomas; 22% of cases of peritoneal serous carcinomatosis were of peritoneal origin; <3% of cases were mucinous carcinomas; and only one malignant Brenner tumor (0.5%) and no pure transitional cell carcinomas were identified. If peritoneal carcinomas, carcinosarcomas, and mixed carcinomas with a serous component are combined with serous carcinomas, this group accounts for 78% of all cases and 87% of advanced stage cases, suggesting a greater uniformity to epithelial ovarian cancer than previously appreciated.

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Author and article information

Contributors

Yu Zhang

Yan Tian

Jing-Jing Yu

Jie He

Jia Luo

Sai Zhang

Cen-E Tang

Yi-ming Tao

Journal

Journal ID (nlm-ta): J Ovarian Res

Journal ID (iso-abbrev): J Ovarian Res

Title: Journal of Ovarian Research

Publisher: BioMed Central

ISSN (Electronic): 1757-2215

Publication date Collection: 2013

Publication date (Electronic): 30 July 2013

Volume: 6

Page: 55

Affiliations

[1 ]Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan, China

[2 ]Department of Surgical Oncology, Hunan Cancer Hospital, The Affiliated Hospital of Xiangya Medical College, Changsha, Hunan, China

[3 ]Institute of Medical Sciences, Major Human Disease Tissue Bank, Xiangya Hospital, Central South University, Changsha, Hunan, China

Article

Publisher ID: 1757-2215-6-55

DOI: 10.1186/1757-2215-6-55

PMC ID: 3737014

PubMed ID: 23898938

SO-VID: c99933dd-25da-4ce7-95c3-e584e35d982e

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Overexpression of WDR62 is associated with centrosome amplification in human ovarian cancer

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Abstract

Purpose

Materials and methods

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Most cited references 17

Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy.

Whole exome sequencing identifies recessive WDR62 mutations in severe brain malformations

The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin.

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