Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas
Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas
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DOI：
10.1038/sj.leu.2404529
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发表时间：
2007-03-01
期刊：
影响因子：
11.4
通讯作者：
Tilly, H.
中科院分区：
文献类型：
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作者：
Bertrand, P.;Bastard, C.;Tilly, H.
染色体易位连接免疫球蛋白（IG）和MYC基因已被广泛报道，在伯基特和非伯基特淋巴瘤，但数据有关MYC重排与非IG合作伙伴是稀缺的。在这项研究中，8q24断点涉及非IG位点的17个B细胞淋巴瘤定位荧光原位杂交（FISH）。在7个病例中，断裂点位于MYC周围的一个小区域内：在1个t（7; 8）（p12; q24）和2个t（3; 8）（q27; q24）中，它位于MYC的端粒，而在4个病例中，1个t（2; 8）（p15; q24）和3个t（8; 9）（q24; p13）位于MYC周围的85 kb区域。在这7个病例中，通过FISH鉴定的伴侣区域包含已知参与淋巴瘤发生的基因，即BCL 6、BCL 11A、PAX5和IKAROS。断裂点克隆在两个t（8; 9）（q24; p13）中，位于MYC下游2.5和7kb处，以及位于9号染色体上PAX5下游数百kb处，将MYC连接到ZCCHC7和ZBTB5外显子2，这两个基因编码锌指蛋白。在这7例患者中，通过定量逆转录-聚合酶链反应（RT-PCR）测定的MYC表达显著高于无8q24重排的患者（P = 0.006）。这些结果表明，这些重排是一个非随机过程的结果，靶向MYC与非IG基因参与淋巴细胞分化和淋巴瘤进展。
Chromosomal translocations joining the immunoglobulin (IG) and MYC genes have been extensively reported in Burkitt's and non-Burkitt's lymphomas but data concerning MYC rearrangements with non-IG partners are scarce. In this study, 8q24 breakpoints from 17 B-cell lymphomas involving non-IG loci were mapped by fluorescence in situ hybridization ( FISH). In seven cases the breakpoint was inside a small region encompassing MYC: in one t(7;8)(p12;q24) and two t(3;8)(q27;q24), it was telomeric to MYC whereas in four cases, one t(2;8)(p15;q24) and three t(8;9)(q24;p13) it was located in a 85 kb region encompassing MYC. In these seven cases, partner regions identified by FISH contained genes known to be involved in lymphomagenesis, namely BCL6, BCL11A, PAX5 and IKAROS. Breakpoints were cloned in two t( 8; 9)( q24; p13), 2.5 and 7 kb downstream from MYC and several hundred kb 50 to PAX5 on chromosome 9, joining MYC to ZCCHC7 and to ZBTB5 exon 2, two genes encoding zinc-finger proteins. In these seven cases, MYC expression measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) was significantly higher when compared to that of patients without 8q24 rearrangement (P = 0.006). These results suggest that these rearrangements are the consequence of a non-random process targeting MYC together with non-IG genes involved in lymphocyte differentiation and lymphoma progression.