Three aberrant splicing variants of the HMGIC gene transcribed in uterine leiomyomas

Citation
K. Kurose et al., Three aberrant splicing variants of the HMGIC gene transcribed in uterine leiomyomas, GENE CHROM, 30(2), 2001, pp. 212-217
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
GENES CHROMOSOMES & CANCER
ISSN journal
1045-2257 → ACNP
Volume
30
Issue
2
Year of publication
2001
Pages
212 - 217
Database
ISI
SICI code
1045-2257(200102)30:2<212:TASVOT>2.0.ZU;2-S
Abstract
Cytogenetic aberrations involving chromosome region 12q13-15 occur frequent ly among benign mesenchymal tumors in humans, e.g., pleomorphic adenomas of the parotid gland, pulmonary chondroid hamartomas, lipomas, or uterine lei omyomas. HMGIC, a gene encoding a protein of the high-mobility group, has b een identified as a target of those events. Using the 3' rapid amplificatio n of cDNA ends (RACE) technique, we identified six different fusion transcr ipts of the HMGIC gene among 13 uterine leiomyomas; three of these variants had not been described before. Radiation-hybrid mapping located all three of the novel fusion transcripts in the same chromosomal region as the HMGIC gene. Cloning of the entire HMGIC gene in a genomic contig of PI-derived a rtificial chromosomes and cosmids revealed that the 3' portion of each nove l fusion transcript contained cryptic exonic sequences (designated a, b, an d c) present in intron 3 of the HMGIC gene. Thus, aberrant alternative spli cing was responsible for abnormal HMGIC isoforms in those myomas. Identific ation of these novel variants suggested that aberrant splicing can join chr omosomal translocation and inversion as a mechanism for producing abnormal HMGIC transcripts, and that separation of the DNA binding domains of HMGIC from its acidic carboxyl-terminal regulatory domain can lead to development of benign mesenchymal tumors. (C) 2001 Wiley-Liss, Inc.