Translocation breakpoints upstream of the HMGIC gene in uterine leiomyomata suggest dysregulation of this gene by a mechanism different from that in lipomas.
Uterine leiomyomata are the most common pelvic tumors in women and are the indication for more than 200,000 hysterectomies annually in the United States. Rearrangement of chromosome 12 in bands q14-q15 is characteristic of uterine leiomyomata and other benign mesenchymal tumors, and we identified a yeast artificial chromosome (YAC) spanning chromosome 12 translocation breakpoints in a uterine leiomyoma, a pulmonary chondroid hamartoma, and a lipoma. Recently, we demonstrated that HMGIC, which is an architectural factor mapping within the YAC, is disrupted in lipomas, resulting in novel fusion transcripts. Here, we report on the localization of translocation breakpoints in seven uterine leiomyomata from 10 to > 100 kb upstream of HMGIC by use of fluorescence in situ hybridization. Our findings suggest a different pathobiologic mechanism in uterine leiomyomata from that in lipomas. HMGIC is the first gene identified in chromosomal rearrangements in uterine leiomyomata and has important implications for an understanding of benign mesenchymal proliferation and differentiation.
Schoenberg Fejzo
M
M
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
Ashar
H R
HR
Krauter
K S
KS
Powell
W L
WL
Rein
M S
MS
Weremowicz
S
S
Yoon
S J
SJ
Kucherlapati
R S
RS
Chada
K
K
Morton
C C
CC
D002881:Chromosomes, Human, Pair 12; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007889:Leiomyoma / Q000235:genetics*; D008067:Lipoma / Q000235:genetics*; D014178:Translocation, Genetic; D014594:Uterine Neoplasms / Q000235:genetics*