High Frequency of Ovarian Cyst Development in Vhl2B/+;Snf5+/− Mice

Yasumichi Kuwahara, Leslie M. Kennedy, Anthony Karnezis, E. Lorena Mora-Blanco, Arlin B. Rogers, Christopher D. Fletcher, David G. Huntsman, Charles W.M. Roberts, W. Kimryn Rathmell, Bernard E. Weissman

Research output: Contribution to journalArticle

Abstract

The new paradigm of mutations in chromatin-modifying genes as driver events in the development of cancers has proved challenging to resolve the complex influences over disease phenotypes. In particular, impaired activities of members of the SWI/SNF chromatin remodeling complex have appeared in an increasing variety of tumors. Mutations in SNF5, a member of this ubiquitously expressed complex, arise in almost all cases of malignant rhabdoid tumor in the absence of additional genetic alterations. Therefore, we studied how activation of additional oncogenic pathways might shift the phenotype of disease driven by SNF5 loss. With the use of a genetically engineered mouse model, we examined the effects of a hypomorphic Vhl2B allele on disease phenotype, with a modest up-regulation of the hypoxia response pathway. Snf5+/−;Vhl2B/+ mice did not demonstrate a substantial difference in overall survival or a change in malignant rhabdoid tumor development. However, a high percentage of female mice showed complex hemorrhagic ovarian cysts, a phenotype rarely found in either parental mouse strain. These lesions also showed mosaic expression of SNF5 by immunohistochemistry. Therefore, our studies implicate that modest changes in angiogenic regulation interact with perturbations of SWI/SNF complex activity to modulate disease phenotypes.

Original languageEnglish (US)
Pages (from-to)1510-1516
Number of pages7
JournalAmerican Journal of Pathology
Volume188
Issue number7
DOIs
StatePublished - Jul 1 2018
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kuwahara, Y., Kennedy, L. M., Karnezis, A., Mora-Blanco, E. L., Rogers, A. B., Fletcher, C. D., Huntsman, D. G., Roberts, C. W. M., Rathmell, W. K., & Weissman, B. E. (2018). High Frequency of Ovarian Cyst Development in Vhl2B/+;Snf5+/− Mice. American Journal of Pathology, 188(7), 1510-1516. https://doi.org/10.1016/j.ajpath.2018.03.010