PMID- 11733348 OWN - NLM STAT- MEDLINE DCOM- 20011218 LR - 20191210 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 159 IP - 6 DP - 2001 Dec TI - BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). PG - 1987-92 AB - Translocation t(15;19)(q13;p13.1) defines a lethal midline carcinoma arising adjacent to respiratory tract in young people. To characterize molecular alterations responsible for the distinctly aggressive biological behavior of this cancer, we mapped the chromosome 15 and 19 translocation breakpoints by fluorescence in situ hybridization (FISH) and Southern blotting. To evaluate preliminarily the frequency, anatomical distribution, and histological features of t(15;19) cancer, we developed a FISH assay for paraffin sections. Our findings reveal a novel oncogenic mechanism in which the chromosome 19 translocation breakpoint interrupts the coding sequence of a bromodomain gene, BRD4. These studies implicate BRD4 as a potential partner in a t(15;19)-associated fusion oncogene. In addition, we localized the chromosome 15 breakpoint to a 9-kb region in each of two cases, thereby identifying several candidate oncogenes which might represent the BRD4 fusion partner. FISH evaluation of 13 pediatric carcinomas revealed t(15;19) in one of four sinonasal carcinomas, whereas this translocation was not detected in thymic (n = 3), mucoepidermoid (n = 3), laryngeal (n = 2), or nasopharyngeal (n = 1) carcinomas. Our studies shed light on the oncogenic mechanism underlying t(15;19) and provide further evidence that this highly lethal cancer arises from respiratory mucosa. FAU - French, C A AU - French CA AD - Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. cafrench@bics.bwh.harvard.edu FAU - Miyoshi, I AU - Miyoshi I FAU - Aster, J C AU - Aster JC FAU - Kubonishi, I AU - Kubonishi I FAU - Kroll, T G AU - Kroll TG FAU - Dal Cin, P AU - Dal Cin P FAU - Vargas, S O AU - Vargas SO FAU - Perez-Atayde, A R AU - Perez-Atayde AR FAU - Fletcher, J A AU - Fletcher JA LA - eng SI - GENBANK/AF386649 GR - T32-HLO7627/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (BRD4 protein, human) RN - 0 (Cell Cycle Proteins) RN - 0 (DNA, Neoplasm) RN - 0 (Nuclear Proteins) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Protein Isoforms) RN - 0 (Transcription Factors) SB - IM CIN - Am J Pathol. 2001 Dec;159(6):1979-80. PMID: 11733346 MH - Adolescent MH - Adult MH - Alternative Splicing MH - Blotting, Southern MH - Carcinoma, Squamous Cell/genetics/pathology MH - Cell Cycle Proteins MH - Child MH - Child, Preschool MH - Chromosomes, Human, Pair 15/*genetics MH - Chromosomes, Human, Pair 19/*genetics MH - DNA, Neoplasm/genetics MH - Female MH - Gene Rearrangement/*genetics MH - Genes/genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*genetics/pathology MH - Male MH - Middle Aged MH - Molecular Sequence Data MH - Nuclear Proteins MH - Oncogene Proteins, Fusion/*genetics MH - Protein Isoforms/genetics MH - Transcription Factors MH - *Translocation, Genetic MH - Tumor Cells, Cultured PMC - PMC1850578 EDAT- 2001/12/26 10:00 MHDA- 2002/01/05 10:01 PMCR- 2002/06/01 CRDT- 2001/12/26 10:00 PHST- 2001/12/26 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/12/26 10:00 [entrez] PHST- 2002/06/01 00:00 [pmc-release] AID - S0002-9440(10)63049-0 [pii] AID - 2953 [pii] AID - 10.1016/S0002-9440(10)63049-0 [doi] PST - ppublish SO - Am J Pathol. 2001 Dec;159(6):1987-92. doi: 10.1016/S0002-9440(10)63049-0.