Charité, CBF, Med. Klinik für Hämatologie, Onkologie, Berlin, Germany.
Genes Chromosomes Cancer. 2012 Mar;51(3):290-9. doi: 10.1002/gcc.21915. Epub 2011 Nov 25.
Burkitt lymphoma and a subset of diffuse large B-cell lymphomas are characterized by chromosomal alterations affecting the MYC oncogene on 8q24. In most cases MYC is found juxtaposed to the immunoglobulin heavy chain (IGH) gene locus. Translocations to the immunoglobulin kappa (IGK) gene locus on 2p11 are observed in around 5-10% of cases. Little data exist on the molecular mechanisms leading to this aberration. The chromosomal breakpoints on chromosome 8 have been found dispersed over a large area 3' of MYC. In order to obtain a better understanding of this chromosomal translocation we developed a long-distance inverse (LDI) PCR method for the identification of chromosomal translocations affecting the IGK locus. We investigated a number of cytogenetically mostly uncharacterized high-grade lymphoma samples and identified a MYC-IGK juxtaposition in seven patients and three t(2;8)-positive cell lines. The chromosomal breakpoints were molecularly characterized and analyzed. The linear distance of the breakpoints on chromosome 8 to MYC ranged from some 100 bp to more than 0.5 MB. The reciprocal translocated allele could be characterized in the majority of cases. This study represents the largest series of t(2;8)-positive cases analyzed so far. The LDI PCR method developed here should also be useful for the analysis of chromosomal translocations affecting the IGK locus in general.
伯基特淋巴瘤和一部分弥漫性大 B 细胞淋巴瘤的特征是染色体改变，影响 8q24 上的 MYC 癌基因。在大多数情况下，MYC 位于免疫球蛋白重链（IGH）基因座附近。在大约 5-10%的病例中观察到 2p11 上的免疫球蛋白 κ（IGK）基因座的易位。关于导致这种异常的分子机制的数据很少。染色体 8 上的染色体断点分散在 MYC 的 3'端的一个大区域上。为了更好地理解这种染色体易位，我们开发了一种长距离反向（LDI）PCR 方法，用于鉴定影响 IGK 基因座的染色体易位。我们研究了一些细胞遗传学上大多未表征的高级别淋巴瘤样本，并在七名患者和三株 t（2；8）阳性细胞系中鉴定出 MYC-IGK 并列。对染色体断点进行了分子特征分析。8 号染色体上的断点与 MYC 的线性距离从大约 100bp 到超过 0.5MB 不等。在大多数情况下，可以对相互易位的等位基因进行特征分析。本研究代表了迄今为止分析的最大系列 t（2；8）阳性病例。这里开发的 LDI PCR 方法也应该对一般影响 IGK 基因座的染色体易位的分析有用。
