Martín-Subero José I, Klapper Wolfram, Sotnikova Anna, Callet-Bauchu Evelyne, Harder Lana, Bastard Christian, Schmitz Roland, Grohmann Susanne, Höppner Jorge, Riemke Jennifer, Barth Thomas F E, Berger Françoise, Bernd Heinz-Wolfram, Claviez Alexander, Gesk Stefan, Frank Georgiy A, Kaplanskaya Irina B, Möller Peter, Parwaresch Reza M, Rüdiger Thomas, Stein Harald, Küppers Ralf, Hansmann Martin L, Siebert Reiner
Institutes of Human Genetics and Hematopathology, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany.
Cancer Res. 2006 Nov 1;66(21):10332-8. doi: 10.1158/0008-5472.CAN-06-1992.
Chromosomal breakpoints affecting immunoglobulin (IG) loci are recurrent in many subtypes of B-cell lymphomas. However, despite the predominant B-cell origin of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL), the presence of chromosomal translocations in IG loci has not yet been systematically explored. Therefore, we have investigated a series of cHL for chromosomal breakpoints in the IGH (n = 230), IGL (n = 139), and IGK (n = 138) loci by interphase cytogenetics. Breakpoints in the IGH, IGL, or IGK locus were observed in the HRS cells of 26 of 149 (17%), 2 of 70, and 1 of 77 evaluable cHLs, respectively. The IG partners could be identified in eight cHLs and involved chromosomal bands 2p16 (REL), 3q27 (BCL6, two cases), 8q24.1 (MYC), 14q24.3, 16p13.1, 17q12, and 19q13.2 (BCL3/RELB). In 65 of 85 (76%) cHLs evaluable for an IGH triple-color probe, the HRS cells showed evidence for a (partial) deletion of the IGH constant region, suggesting the presence of class switch recombination (CSR). Furthermore, analyses with this probe in cases with IGH breakpoints indicated that at least part of them seem to be derived from CSR defects. Our results show that chromosomal breakpoints affecting the IG loci are recurrent in cHL.
影响免疫球蛋白（IG）基因座的染色体断点在许多B细胞淋巴瘤亚型中很常见。然而，尽管经典霍奇金淋巴瘤（cHL）中霍奇金和里德-斯特恩伯格（HRS）细胞主要起源于B细胞，但IG基因座中染色体易位的存在尚未得到系统研究。因此，我们通过间期细胞遗传学研究了一系列cHL的IGH（n = 230）、IGL（n = 139）和IGK（n = 138）基因座中的染色体断点。在149例可评估的cHL中，分别有26例（17%）、70例中的2例和77例中的1例HRS细胞中观察到IGH、IGL或IGK基因座的断点。在8例cHL中可鉴定出IG伙伴，涉及染色体带2p16（REL）、3q27（BCL6，2例）、8q24.1（MYC）、14q24.3、16p13.1、17q12和19q13.2（BCL3/RELB）。在85例可评估IGH三色探针的cHL中，有65例（76%）HRS细胞显示IGH恒定区（部分）缺失的证据，提示存在类别转换重组（CSR）。此外，对有IGH断点的病例用该探针进行分析表明，其中至少部分似乎源于CSR缺陷。我们结果表明，影响IG基因座的染色体断点在cHL中很常见。
