Atayar Ciğdem, Kok Klaas, Kluiver Joost, Bosga Anneke, van den Berg Eva, van der Vlies Pieter, Blokzijl Tjasso, Harms Geert, Davelaar Inge, Sikkema-Raddatz Birgit, Martin-Subero Jose Ignacio, Siebert Reiner, Poppema Sibrand, van den Berg Anke
Department of Pathology and Laboratory Medicine, University Medical Centre Groningen and University of Groningen 9700 RB, The Netherlands.
Hum Pathol. 2006 Jun;37(6):675-83. doi: 10.1016/j.humpath.2006.01.018.
DEV is the only cell line derived from nodular lymphocyte predominance type of Hodgkin's lymphoma (NLPHL); however, a comprehensive report about the genetic and immunophenotypic profile of this unique cell line is lacking. We analyzed DEV with respect to immunophenotype and genetic aberrations. The immunostaining revealed positivity for CD45, CD20, CD22, CD79a, IgA2, CD80, CD86, CD74, and BCL6. Cytogenetically, DEV has complex chromosome 3 translocations involving chromosomes 7, 14, and 22. A detailed analysis of the 3q27 breakpoint of the der(3)t(3;14)(p14;q32)t(3;22)(q27;q11.2) revealed a break in the BCL6 alternative breakpoint region. Using array comparative genomic hybridization, a 3-megabase homozygous deletion at 17q24.1-24.2 was identified. Fluorescence in situ hybridization indicated the presence of 2 chromosome 17 homologues, each of which carried a small interstitial deletion. Eight microsatellite markers flanking the homozygously deleted region all showed a homozygous pattern suggesting loss of one of the parental alleles. D17S1809 and D17S1816 could not be amplified using DEV DNA, in keeping with a location within the homozygously deleted segment. In conclusion, DEV has an immunophenotype that is consistent with the neoplastic cells of NLPHL cases, the lymphocytic and histiocytic cells. We demonstrated involvement of the BCL6 gene based on the presence of a breakpoint in the alternative breakpoint region and nuclear staining for BCL6 protein and identified a homozygously deleted region at 17q24.
DEV是唯一源自结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）的细胞系；然而，关于这一独特细胞系的基因和免疫表型特征的全面报告尚付阙如。我们分析了DEV的免疫表型和基因畸变情况。免疫染色显示其对CD45、CD20、CD22、CD79a、IgA2、CD80、CD86、CD74和BCL6呈阳性。细胞遗传学分析表明，DEV存在涉及7号、14号和22号染色体的复杂3号染色体易位。对der(3)t(3;14)(p14;q32)t(3;22)(q27;q11.2)的3q27断点进行详细分析后发现，BCL6可变断点区域存在断裂。利用阵列比较基因组杂交技术，在17q24.1 - 24.2处鉴定出一个3兆碱基的纯合缺失。荧光原位杂交显示存在2条17号染色体同源物，每条同源物都带有一个小的间质缺失。位于纯合缺失区域两侧的8个微卫星标记均显示为纯合模式，提示一个亲本等位基因缺失。使用DEV DNA无法扩增D17S1809和D17S1816，这与它们位于纯合缺失片段内的位置相符。总之，DEV的免疫表型与NLPHL病例的肿瘤细胞（淋巴细胞和组织细胞）一致。基于可变断点区域存在断点以及BCL6蛋白的核染色情况，我们证实了BCL6基因受累，并在17q24处鉴定出一个纯合缺失区域。
