Abstract 3010: Meiotic cohesin REC8 associates with chromosome instability in melanoma

Abstract

Abstract Chromosome instability (CIN) is an important component of multiple malignancies. CIN is linked to drug resistance, tumor grade and aggressiveness. Melanoma is a highly chromosome instable tumor and CIN is a differentiating feature between melanoma and benign nevi. Meiotic proteins are present in melanoma and previous work in our lab suggests a role for these proteins in CIN and that melanoma cell replication has attributes as chromosome pairing and DNA bridging that can be explained by the presence of meiosis proteins. REC8 is a meiotic cohesin which holds sister chromatids together during the first meiotic division, therefore we sought to study the potential role for REC8 in CIN in Melanoma. A model of chromosome instability developed in melanocytic cell lines showed association of REC8 as CIN progressed strengthening the hypothesis that REC8 may be involved in CIN. We overexpressed REC8 in melanoma lines and in E6E7 melanocytes with a TET-inducible system and examined the change in the polyploid population by flow cytometry, cell count and FISH. Results suggest that overexpression of REC8 alone is not sufficient to drive polyploidy in these cell lines. Nevertheless, the association of REC8 with CIN is intriguing and further research in the role of meiosis proteins in melanoma is warranted. Future work will aim at dissecting coexisting meiotic proteins; specially the proteins of the cohesin ring and its regulatory proteins that are also present at high levels in melanoma and could be responsible of chromosome number abnormalities. Citation Format: Julia Escandon, Scott Lindsey, Mark S Eller, James M Grichnik. Meiotic cohesin REC8 associates with chromosome instability in melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3010. doi:10.1158/1538-7445.AM2015-3010