An Qian, Wright Sarah L, Moorman Anthony V, Parker Helen, Griffiths Mike, Ross Fiona M, Davies Teresa, Harrison Christine J, Strefford Jon C
Cancer Sciences Division, University of Southampton, Southampton, UK.
Haematologica. 2009 Aug;94(8):1164-9. doi: 10.3324/haematol.2008.002808. Epub 2009 Jul 7.
The dic(9;20)(p11-13;q11) is a recurrent chromosomal abnormality in patients with acute lymphoblastic leukemia. Although it results in loss of material from 9p and 20q, the molecular targets on both chromosomes have not been fully elucidated. From an initial cohort of 58 with acute lymphoblastic leukemia patients with this translocation, breakpoint mapping with fluorescence in situ hybridization on 26 of them revealed breakpoint heterogeneity of both chromosomes. PAX5 has been proposed to be the target gene on 9p, while for 20q, FISH analysis implicated the involvement of the ASXL1 gene, either by a breakpoint within (n=4) or centromeric (deletion, n=12) of the gene. Molecular copy-number counting, long-distance inverse PCR and direct sequence analysis identified six dic(9;20) breakpoint sequences. In addition to the three previously reported: PAX5-ASXL1, PAX5-C20ORF112 and PAX5-KIF3B; we identified three new ones in this study: sequences 3' of PAX5 disrupting ASXL1, and ZCCHC7 disrupted by sequences 3' of FRG1B and LOC1499503. This study provides insight into the breakpoint complexity underlying dicentric chromosomal formation in acute lymphoblastic leukemia and highlights putative target gene loci.
dic(9;20)(p11 - 13;q11)是急性淋巴细胞白血病患者中一种常见的染色体异常。尽管它导致9p和20q的物质丢失，但两条染色体上的分子靶点尚未完全阐明。在最初的58例患有这种易位的急性淋巴细胞白血病患者队列中，对其中26例进行荧光原位杂交断点作图，结果显示两条染色体均存在断点异质性。PAX5被认为是9p上的靶基因，而对于20q，荧光原位杂交分析表明ASXL1基因参与其中，要么是基因内部的断点（n = 4），要么是着丝粒处（缺失，n = 12）。分子拷贝数计数、长距离反向PCR和直接序列分析确定了六个dic(9;20)断点序列。除了之前报道的三个：PAX5 - ASXL1、PAX5 - C20ORF112和PAX5 - KIF3B；我们在本研究中还确定了三个新的：PAX5 3'端破坏ASXL1的序列，以及FRG1B和LOC1499503 3'端破坏ZCCHC7的序列。这项研究深入了解了急性淋巴细胞白血病中双着丝粒染色体形成背后的断点复杂性，并突出了假定的靶基因位点。
