Abstract 178: RASSF10 is frequently methylated in epithelial cancers
| Autor: | Dion Morton, John D. Minna, Msahiro Yao, Dietmar Krex, Victoria K. Hill, Ivan Bièche, Farida Latif, Eammon R. Maher |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:178-178 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | The classical Ras-association domain family (RASSF1-6) are a group of Ras effector molecules that contain a C-terminal Ras-association (RA) domain of the RalGDS/AF-6 variety and a protein interaction domain known as the Sav/RASSF/Hippo (SARAH) domain. Several members of the classical RASSF family are involved in tumorigenesis since epigenetic inactivation of many isoforms is a frequent event across many tumor types and their functions are consistent with roles as tumor suppressor proteins. Recently several additional RA-domain containing family members have been identified and designated N-terminal RASSF proteins (RASSF7-10). These comprise RASSF7 (also known as HRC1 located 11p15.5), RASSF8 (also known as HOJ-1 or C12ORF2 located 12p12.1), RASSF9 (also known as P-CIP1 or PAMCI located 12q21.31) and RASSF10 (located 11p15.2). These proteins are divergent and structurally distinct from RASSF1-6, containing an RA domain within their extreme N-termini and lacking the SARAH protein interaction domain. Little is known about the N-terminal RASSF7-10 proteins although they represent an evolutionarily conserved group of proteins with orthologues of all four in the lower vertebrate Xenopus laevis and a RASSF7/8 homologue in Drosophila melanogaster distinct from the RASSF1-6 Drosophila homologue. We have recently characterized the N-terminal RASSF10 gene and demonstrated frequent methylation of the associated 5’ CpG island in acute lymphoblastic leukemia. In this report we analysed the methylation status of the CpG island in a range of common epithelial cancers. RASSF10 was frequently methylated in grade II-IV gliomas (grade II, 50%; grade III, 80%, grade IV 57%) but was unmethylated in grade I astrocytomas and in DNA from age matched control brain samples. In other common epithelial cancers RASSF10 was also methylated but at a lesser frequency compared to grade II-IV gliomas. RASSF10 was methylated in 25% breast tumors, 31% of colorectal cancers, 20% lung tumors and 28% of renal cell carcinomas. RASSF10 was unmethylated in DNA from corresponding normal tissues or control tissue samples. This work demonstrates that RASSF10 is a frequent target of epigenetic inactivation in a range of epithelial cancers as well as haematological cancers. We are now undertaking biological characterization of this novel protein. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 178. |
| Databáze: | OpenAIRE |
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