BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19)

Citation
Ca. French et al., BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19), AM J PATH, 159(6), 2001, pp. 1987-1992
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
0002-9440 → ACNP
Volume
159
Issue
6
Year of publication
2001
Pages
1987 - 1992
Database
ISI
SICI code
0002-9440(200112)159:6<1987:BBGRIA>2.0.ZU;2-B
Abstract
Translocation t(15;19)(q13;p13.1) defines a lethal midline carcinoma arisin g adjacent to respiratory tract in young people. To characterize molecular alterations responsible for the distinctly aggressive biological behavior o f this cancer, we mapped the chromosome 15 and 19 translocation breakpoints by fluorescence in situ hybridization (FISH) and Southern blotting. To eva luate preliminarily the frequency, anatomical distribution, and histologica l features of t(15;19) cancer, we developed a FISH assay for paraffin secti ons. Our findings reveal a novel oncogenic mechanism in which the chromosom e 19 translocation breakpoint interrupts the coding sequence of a bromodoma in gene, BRD4. These studies implicate BRD4 as a potential partner in a t(1 5;19)-associated fusion oncogene. In addition, we localized the chromosome 15 breakpoint to a 9-kb region In each of two cases, thereby identifying se veral candidate oncogenes which might represent the BRD4 fusion partner. FI SH evaluation of 13 pediatric carcinomas revealed t(15;19) in one of four s inonasal 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 arise s from respiratory mucosa.