Abstract

A crucial role of segmental duplications (SDs) of the human genome has been shown in chromosomal rearrangements associated with several genomic disorders. Limited knowledge is yet available on the molecular processes resulting in chromosomal rearrangements in tumors. The t(9;22)(q34;q11) rearrangement causing the 5'BCR/3'ABL gene formation has been detected in more than 90% of cases with chronic myeloid leukemia (CML). In 10-18% of patients with CML, genomic deletions were detected on der(9) chromosome next to translocation breakpoints. The molecular mechanism triggering the t(9;22) and deletions on der(9) is still speculative. Here we report a molecular cytogenetic analysis of a large series of patients with CML with der(9) deletions, revealing an evident breakpoint clustering in two regions located proximally to ABL and distally to BCR, containing an interchromosomal duplication block (SD_9/22). The deletions breakpoints distribution appeared to be strictly related to the distance from the SD_9/22. Moreover, bioinformatic analyses of the regions surrounding the SD_9/22 revealed a high Alu frequency and a poor gene density, reflecting genomic instability and susceptibility to rearrangements. On the basis of our results, we propose a three-step model for t(9;22) formation consisting of alignment of chromosomes 9 and 22 mediated by SD_9/22, spontaneous chromosome breakages and misjoining of DNA broken ends.Oncogene advance online publication, 25 January 2010; doi:10.1038/onc.2009.524.

Autore Pugliese

• Albano Francesco , Specchia Giorgina , Anelli Luisa

Tutti gli autori

• ZAGARIA A.;ALBANO F.;SPECCHIA G.;ANELLI L.;ROCCHI M.;D'ADDABBO P.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2010

ISSN

0950-9232

ISBN

Non Disponibile

Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

21

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

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Codici ASJC

Non Disponibile