Cancer-specific chromosome alterations in the constitutive fragile region FRA3B

Koshi Mimori, Teresa Druck, Hiroshi Inoue, Hansjuerg Alder, Lori Berk, Masaki Mori, Kay Huebner, Carlo M. Croce

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

We have sequenced 870 kilobases of the FHIT/FRA3B locus, from FHIT intron 3 to intron 7. The locus is AT rich (61.5%) and Alu poor (6.2%), and it apparently does not harbor other genes. In a detailed analysis of the 308- kilobase region between FHIT exon 5 and the telomeric end of intron 3, a region known to encompass a human papillomavirus-16 integration site and two clusters of aphidicolin-induced chromosome 3p14.2 breakpoints, we have precisely mapped 10 deletion and translocation endpoints in cancer-derived cell lines relative to positions of specific repetitive elements, regions of high genome flexibility and aphidicolin-induced breakpoints. Conclusions are (i) that aphidicolin-induced breakpoint clusters fall close to high- flexibility sequences, suggesting that these sequences contribute directly to aphidicolin-induced fragility; (ii) that 9 of the 10 FH1T allelic deletions in cancer cell lines resulted in loss of exons, with 7 deletion endpoints near long interspersed nuclear elements or long terminal repeat elements; and (iii) that cancer-specific deletions encompass multiple high-flexibility genomic regions, suggesting that fragile breaks may occur at these regions, whereas repair of the breaks involves homologous pairing of flanking sequences with concomitant deletion of the damaged fragile sequence.

Original languageEnglish
Pages (from-to)7456-7461
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number13
DOIs
Publication statusPublished - Jun 22 1999

All Science Journal Classification (ASJC) codes

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