title: Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest.
abstract: In search of tumor suppressor genes in papillary thyroid carcinoma (PTC), we previously used gene expression profiling to identify genes underexpressed in tumor compared with paired unaffected tissue. While searching for loss of heterozygosity (LOH) in genomic regions harboring candidate tumor suppressor genes, we detected LOH in a approximately 20 kb region around marker D9S176. Several ESTs flanking D9S176 were underexpressed in PTC tumors, and for one of the ESTs, downregulation was highly associated with the activating BRAF mutation V600E, the most common genetic lesion in PTC. A novel gene, NAMA, (noncoding RNA associated with MAP kinase pathway and growth arrest) containing the affected EST was cloned and characterized. NAMA is weakly expressed in several human tissues, and the spliced forms are primarily detected in testis. Several characteristics of NAMA suggest that it is a nonprotein coding but functional RNA; it has no long open reading frames (ORFs); the exons exhibit low sequence identity in the evolutionarily conserved regions; it is inducible by knockdown of BRAF, inhibition of the MAP kinase pathway, growth arrest and DNA damage in cancer cell lines. We suggest that NAMA is a noncoding RNA associated with growth arrest.
authors.affiliation: Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. albert.delachapelle@osumc.edu
authors.forename: Heejei
authors.initials: H
authors.lastname: Yoon
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nagy
authors.forename: Ramana
authors.initials: R
authors.lastname: Davuluri
authors.forename: Saul
authors.initials: S
authors.lastname: Suster
authors.forename: Daniel
authors.initials: D
authors.lastname: Schoenberg
authors.forename: Natalia
authors.initials: N
authors.lastname: Pellegata
authors.forename: Albert de la
authors.initials: Ade L
authors.lastname: Chapelle
mesh_terms: D017209:Apoptosis; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D019656:Loss of Heterozygosity; D020935:MAP Kinase Signaling System; D008297:Male; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D022661:RNA, Untranslated; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D022661:RNA, Untranslated; D012313:RNA; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf