Mao Xin, Onadim Zerrin, Price Elizabeth A, Child Fiona, Lillington Debra M, Russell-Jones Robin, Young Bryan D, Whittaker Sean
Skin Tumour Unit, St John's Institute of Dermatology, 4th Floor, South Wing Block 7, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
J Invest Dermatol. 2003 Sep;121(3):618-27. doi: 10.1046/j.1523-1747.2003.12406.x.
Natural killer and natural killer-like T cell lymphomas represent a rare type of non-Hodgkin's lymphoma originally described to involve the upper aerodigestive tract. This malignancy has been increasingly observed in other extranodal sites, particularly in the skin. Patients with cutaneous natural killer cell lymphoma generally have a poor prognosis; however, the etiology and the underlying molecular pathogenesis remain unclear. This study aimed to investigate comprehensively genomic changes in blastic natural killer and extranodal natural killer-like T cell lymphoma with cutaneous involvement. Comparative genomic hybridization showed chromosome imbalances in six of eight cases studied (75%). The mean number of chromosome imbalances per sample was 2.18+/-1.63 with similar number of gains (1.18+/-1.17) and losses (1.00+/-1.34). The most frequent DNA copy number changes observed were losses of 9/9p (83%), followed by loss of 13q and gain of 7 (67%). Similar patterns of chromosome imbalances were observed in both blastic natural killer and cutaneous natural killer-like T cell lymphomas. Loss of the RB1 gene at 13q14.2 was detected in one blastic natural killer cell lymphoma with 13q loss using a gene dosage assay, and in one cutaneous natural killer-like T cell lymphoma without 13q loss using fluorescent in situ hybridization. Genomic microarray analysis identified oncogene copy number gains of PAK1 and JUNB in three of four cases studied, and gains of RAF1, CTSB, FGFR1, and BCR in two cases. Real-time polymerase chain reaction detected amplification of CTSB and RAF1 in four of five cases analyzed, JUNB and MYCN in three cases, and REL and YES1 in two cases, respectively. In conjunction with this study, an extensive literature search for the published G-banded karyotypes of four subsets of natural killer cell lymphomas was conducted, which showed a nonrandom pattern of multiple chromosome aberrations. These results reveal consistent genetic alterations in cutaneous natural killer cell lymphomas, and provide a basis for further investigation of molecular pathogenesis in this malignancy.
自然杀伤细胞和自然杀伤样T细胞淋巴瘤是一种罕见的非霍奇金淋巴瘤，最初被描述为累及上呼吸道消化道。这种恶性肿瘤在其他结外部位越来越多地被观察到，尤其是在皮肤。皮肤自然杀伤细胞淋巴瘤患者的预后通常较差；然而，其病因和潜在的分子发病机制仍不清楚。本研究旨在全面调查累及皮肤的母细胞性自然杀伤细胞和结外自然杀伤样T细胞淋巴瘤的基因组变化。比较基因组杂交显示，在所研究的8例病例中有6例（75%）存在染色体不平衡。每个样本的染色体不平衡平均数为2.18±1.63，增益（1.18±1.17）和缺失（1.00±1.34）数量相似。观察到的最常见的DNA拷贝数变化是9/9p缺失（83%），其次是13q缺失和7号染色体增益（67%）。在母细胞性自然杀伤细胞淋巴瘤和皮肤自然杀伤样T细胞淋巴瘤中观察到相似的染色体不平衡模式。使用基因剂量分析在1例有13q缺失的母细胞性自然杀伤细胞淋巴瘤中检测到13q14.2处RB1基因缺失，使用荧光原位杂交在1例无13q缺失的皮肤自然杀伤样T细胞淋巴瘤中检测到该缺失。基因组微阵列分析在4例研究病例中有3例鉴定出PAK1和JUNB的癌基因拷贝数增加，2例鉴定出RAF1、CTSB、FGFR1和BCR增加。实时聚合酶链反应分别在5例分析病例中有4例检测到CTSB和RAF1扩增，3例检测到JUNB和MYCN扩增，2例检测到REL和YES1扩增。结合本研究，对已发表的自然杀伤细胞淋巴瘤四个亚组的G带核型进行了广泛的文献检索，结果显示存在多染色体畸变的非随机模式。这些结果揭示了皮肤自然杀伤细胞淋巴瘤中一致的基因改变，并为进一步研究这种恶性肿瘤的分子发病机制提供了基础。
