Non random distribution of genomic features in breakpoint regions involved in chronic myeloid leukemia cases with variant t(9;22) or additional chromosomal rearrangements

Molecular Cancer

Research

Mariano Rocchi¹  Francesco Albano²  Vincenzo Liso²  Luisa Anelli²  Paola Casieri²  Giorgina Specchia²  Antonella Zagaria²  Antonella Russo Rossi²  Nicoletta Coccaro²  Laura Vicari³ 

[1] Department of Genetics and Microbiology, University of Bari, 70126, Bari, Italy;Hematology, University of Bari, 70124, Bari, Italy;Service of Medical Genetics, Cardarelli Hospital, via Cardarelli 9, 80131, Naples, Italy;

关键词: Chronic Myeloid Leukemia;    Dasatinib;    Bacterial Artificial Chromosome Clone;    Chronic Myeloid Leukemia Patient;    Breakpoint Region;   

DOI  :  10.1186/1476-4598-9-120

 received in 2010-01-19, accepted in 2010-05-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe t(9;22)(q34;q11), generating the Philadelphia (Ph) chromosome, is found in more than 90% of patients with chronic myeloid leukemia (CML). As a result of the translocation, the 3' portion of the ABL1 oncogene is transposed from 9q34 to the 5' portion of the BCR gene on chromosome 22 to form the BCR/ABL1 fusion gene. At diagnosis, in 5-10% of CML patients the Ph chromosome is derived from variant translocations other than the standard t(9;22).ResultsWe report a molecular cytogenetic study of 452 consecutive CML patients at diagnosis, that revealed 50 cases identifying three main subgroups: i) cases with variant chromosomal rearrangements other than the classic t(9;22)(q34;q11) (9.5%); ii) cases with cryptic insertions of ABL1 into BCR, or vice versa (1.3%); iii) cases bearing additional chromosomal rearrangements concomitant to the t(9;22) (1.1%). For each cytogenetic group, the mechanism at the basis of the rearrangement is discussed.All breakpoints on other chromosomes involved in variant t(9;22) and in additional rearrangements have been characterized for the first time by Fluorescence In Situ Hybridization (FISH) experiments and bioinformatic analyses. This study revealed a high content of Alu repeats, genes density, GC frequency, and miRNAs in the great majority of the analyzed breakpoints.ConclusionsTaken together with literature data about CML with variant t(9;22), our findings identified several new cytogenetic breakpoints as hotspots for recombination, demonstrating that the involvement of chromosomes other than 9 and 22 is not a random event but could depend on specific genomic features. The presence of several genes and/or miRNAs at the identified breakpoints suggests their potential involvement in the CML pathogenesis.

【 授权许可】

CC BY   
© Albano et al; licensee BioMed Central Ltd. 2010