Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation

Citation
H. Kanoe et al., Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of Translin and topoisomerase II in the process of translocation, ONCOGENE, 18(3), 1999, pp. 721-729
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
18
Issue
3
Year of publication
1999
Pages
721 - 729
Database
ISI
SICI code
0950-9232(19990121)18:3<721:COGBIT>2.0.ZU;2-P
Abstract
Fusion of TLS/FUS and CHOP gene by reciprocal translocation t(12;16)(q32;q1 6) is a common genetic event found in myxoid and round-cell liposarcomas, C haracterization of this genetic event was performed by three methods, South ern blot, RT-PCR, and genomic long-distance PCR in nine myxoid and three ro und-cell liposarcomas. All but one tumors showed genetic alternations indic ating the fusion of TLS/FUS and CHOP gene, Two novel types of fusion transc ripts were found, of which one lacked exon 2 sequence of CHOP gene, and the other lacked 3' half of exon 5 of TLS gene, The latter case was caused by a cryptic splicing site which,vas created by the genomic fusion, Detailed a nalyses genomic fusion points revealed several sequence characteristics sur rounding the fusion points, Homology analyses of breakpoint sequences with known sequence motifs possibly involve in the process of translocation unco vered Translin binding sequences at both of TLS/ FUS and CHOP breakpoints i n two cases. Translocations were always associated with other genetic alter ations, such as deletions, duplications, or insertions. Short direct repeat s were almost always found at both ends of deleted or duplicated fragments some of which had apparently been created by joining of sequences that flan k the rearrangement. Finally, consensus topoisomerase II cleavage sites wer e found at breakpoints in all cases analysed, suggesting a role of this enz yme in creating staggered ends at the breakpoint, These data suggested that sequence characteristics may play an important role to recruit several fac tors such as Translin and topoisomerase II in the process of chromosomal tr anslation in liposarcomas.