Chui Daniel T Y, Hammond David, Baird Margaret, Shield Lesley, Jackson Robert, Jarrett Ruth F
Leukaemia Research Fund Virus Centre, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.
Genes Chromosomes Cancer. 2003 Oct;38(2):126-36. doi: 10.1002/gcc.10266.
The etiology of Hodgkin lymphoma (HL) is poorly understood, and studies of the genetics of this disease have been hampered by the scarcity of the Hodgkin and Reed-Sternberg (HRS) cells within tumors. To determine whether recurrent genomic imbalances are a feature of HL, CD30-positive HRS cells were laser-microdissected from 20 classical Hodgkin lymphomas (cHLs) and four HL-derived cells lines and subjected to analyses by comparative genomic hybridization. In primary tumors, the most frequently involved chromosomal gains were 17q (70%), 2p (40%), 12q (40%), 17p (40%), 22q (35%), 9p (30%), 14q (30%), and 16p (30%), with minimal overlapping regions at 17q21, 2p23-13, 12q24, 17p13, 22q13, 9p24-23, 14q32, 16p13.3, and 16p11.2. The most frequent losses involved 13q (35%), 6q (30%), 11q (25%), and 4q (25%), with corresponding minimal overlapping regions at 13q21, 6q22, 11q22, and 4q32. Statistical analysis revealed significantly more gains of 2p and 14q in the older adult cases; loss of 13q was associated with a poor outcome. The results suggest that there is a set of recurrent chromosomal abnormalities associated with cHL and provide further evidence that cHL is genetically distinct from nodular lymphocyte predominance Hodgkin lymphoma (NLPHL). Abnormalities of 17q are infrequent in other lymphomas or NLPHL; this finding, coupled with current knowledge of gene expression in cHL, suggests that genes present on 17q may play an important role in the pathogenesis of cHL.
霍奇金淋巴瘤（HL）的病因尚不清楚，对该疾病遗传学的研究因肿瘤中霍奇金和里德-斯腾伯格（HRS）细胞的稀缺而受阻。为了确定复发性基因组失衡是否为HL的一个特征，从20例经典型霍奇金淋巴瘤（cHL）和4株HL衍生细胞系中激光显微切割出CD30阳性的HRS细胞，并通过比较基因组杂交进行分析。在原发性肿瘤中，最常出现的染色体增加包括17q（70%）、2p（40%）、12q（40%）、17p（40%）、22q（35%）、9p（30%）、14q（30%）和16p（30%），在17q21、2p23 - 13、12q24、17p13、22q13、9p24 - 23、14q32、16p13.3和16p11.2处有最小重叠区域。最常见的缺失包括13q（35%）、6q（30%）、11q（25%）和4q（25%），在13q21、6q22、11q22和4q32处有相应的最小重叠区域。统计分析显示，老年病例中2p和14q的增加明显更多；13q缺失与不良预后相关。结果表明，存在一组与cHL相关的复发性染色体异常，并进一步证明cHL在遗传学上与结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）不同。17q异常在其他淋巴瘤或NLPHL中很少见；这一发现，结合目前对cHL基因表达的了解，表明17q上存在的基因可能在cHL的发病机制中起重要作用。
