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.