Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma.
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.
Duns
Gerben
G
Departments of Genetics and Pathology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
van den Berg
Eva
E
van Duivenbode
Inge
I
Osinga
Jan
J
Hollema
Harry
H
Hofstra
Robert M W
RM
Kok
Klaas
K
D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human