Identification of a novel noncoding RNA gene, NAMA, that is downregulated in papillary thyroid carcinoma with BRAF mutation and associated with growth arrest
✍ Scribed by Heejei Yoon; Huiling He; Rebecca Nagy; Ramana Davuluri; Saul Suster; Daniel Schoenberg; Natalia Pellegata; Albert de la Chapelle
- Book ID
- 102862534
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- French
- Weight
- 793 KB
- Volume
- 121
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 ∼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, (__n__oncoding RNA __a__ssociated with __M__AP kinase pathway and growth __a__rrest) 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. © 2007 Wiley‐Liss, Inc.