PMID- 20501857 OWN - NLM STAT- MEDLINE DCOM- 20100617 LR - 20220817 IS - 1538-7445 (Electronic) IS - 0008-5472 (Linking) VI - 70 IP - 11 DP - 2010 Jun 1 TI - Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. PG - 4287-91 LID - 10.1158/0008-5472.CAN-10-0120 [doi] AB - Sporadic clear cell renal cell carcinoma (cRCC) is genetically characterized by the recurrent loss of the short arm of chromosome 3, with a hotspot for copy number loss in the 3p21 region. We applied a method called "gene identification by nonsense-mediated mRNA decay inhibition" to a panel of 10 cRCC cell lines with 3p21 copy number loss to identify biallelic inactivated genes located at 3p21. This revealed inactivation of the histone methyltransferase gene SETD2, located on 3p21.31, as a common event in cRCC cells. SETD2 is nonredundantly responsible for trimethylation of the histone mark H3K36. Consistent with this function, we observed loss or a decrease of H3K36me3 in 7 out of the 10 cRCC cell lines. Identification of missense mutations in 2 out of 10 primary cRCC tumor samples added support to the involvement of loss of SETD2 function in the development of cRCC tumors. CI - Copyright 2010 AACR. FAU - Duns, Gerben AU - Duns G AD - Departments of Genetics and Pathology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands. FAU - van den Berg, Eva AU - van den Berg E FAU - van Duivenbode, Inge AU - van Duivenbode I FAU - Osinga, Jan AU - Osinga J FAU - Hollema, Harry AU - Hollema H FAU - Hofstra, Robert M W AU - Hofstra RM FAU - Kok, Klaas AU - Kok K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100525 PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (RNA, Messenger) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) RN - EC 2.1.1.43 (SETD2 protein, human) SB - IM MH - Adenocarcinoma, Clear Cell/enzymology/*genetics MH - Carcinoma, Renal Cell/enzymology/*genetics MH - Cell Line, Tumor MH - Chromosomes, Human, Pair 3 MH - Comparative Genomic Hybridization MH - DNA Methylation MH - DNA Mutational Analysis MH - Gene Expression Regulation, Enzymologic MH - Gene Expression Regulation, Neoplastic MH - Genes, Tumor Suppressor MH - Histone-Lysine N-Methyltransferase/*genetics MH - Humans MH - Kidney Neoplasms/enzymology/*genetics MH - Oligonucleotide Array Sequence Analysis MH - RNA, Messenger/genetics/metabolism EDAT- 2010/05/27 06:00 MHDA- 2010/06/18 06:00 CRDT- 2010/05/27 06:00 PHST- 2010/05/27 06:00 [entrez] PHST- 2010/05/27 06:00 [pubmed] PHST- 2010/06/18 06:00 [medline] AID - 0008-5472.CAN-10-0120 [pii] AID - 10.1158/0008-5472.CAN-10-0120 [doi] PST - ppublish SO - Cancer Res. 2010 Jun 1;70(11):4287-91. doi: 10.1158/0008-5472.CAN-10-0120. Epub 2010 May 25.