Siu L L, Wong K F, Chan J K, Kwong Y L
Department of Pathology, Queen Elizabeth Hospital, Hong Kong.
Am J Pathol. 1999 Nov;155(5):1419-25. doi: 10.1016/S0002-9440(10)65454-5.
Putative natural killer (NK) cell lymphoma/leukemia is a rare group of recently characterized hematolymphoid malignancies. They are highly aggressive and frequently present in extranodal sites, including the nasal area and the upper aerodigestive system, and nonnasal areas such as the skin and the gastrointestinal tract. According to clinicopathological features, they can be classified into nasal NK cell lymphoma, nasal-type NK cell lymphoma occurring in nonnasal areas, and NK cell lymphoma/leukemia. Genetic alterations in NK cell lymphoma/leukemia are not well defined. In this study, we have performed comparative genomic hybridization (CGH) on DNA extracted from fresh or frozen tissues of 10 patients with NK cell lymphoma/leukemia. They comprised four nasal NK cell lymphomas, one nasal-type NK cell lymphoma, and five NK cell lymphomas/leukemias. CGH showed frequent deletions at 6q16-q27 (four cases), 13q14-q34 (three cases), 11q22-q25 (two cases), 17p13 (two cases), and loss of the whole chromosome X (two cases). DNA amplification was observed in a majority of the chromosomes. Five cases showed DNA gains at region 1p32-pter. Frequent DNA gains were also found in chromosomes 6p, 11q, 12q, 17q, 19p, 20q, and Xp (three cases each). Interestingly, DNA gains were more frequent in nasal/nasal-type NK cell lymphomas than NK cell lymphoma/leukemia. These genetic alterations correlated well with karyotypic features found in some of the cases. The frequent DNA losses at 6q and 13q suggest that the presence of tumor suppressor genes at these regions is important in NK cell transformation. In addition to establishing novel patterns of genomic imbalances in these rare NK cell malignancies, which may be targets for future molecular analysis, this study also provides important information on genetic alterations in NK cell lymphomas that may be useful in defining their positions in current lymphoma classification schemes, which are increasingly focusing on phenotypic and genotypic correlations.
推定自然杀伤（NK）细胞淋巴瘤/白血病是一组罕见的、最近才得以明确特征的血液淋巴系统恶性肿瘤。它们具有高度侵袭性，常出现于结外部位，包括鼻腔区域和上呼吸消化道系统，以及非鼻腔部位，如皮肤和胃肠道。根据临床病理特征，它们可分为鼻腔NK细胞淋巴瘤、发生于非鼻腔部位的鼻型NK细胞淋巴瘤以及NK细胞淋巴瘤/白血病。NK细胞淋巴瘤/白血病中的基因改变尚未明确界定。在本研究中，我们对从10例NK细胞淋巴瘤/白血病患者的新鲜或冷冻组织中提取的DNA进行了比较基因组杂交（CGH）分析。这些患者包括4例鼻腔NK细胞淋巴瘤、1例鼻型NK细胞淋巴瘤和5例NK细胞淋巴瘤/白血病。CGH显示在6q16 - q27（4例）、13q14 - q34（3例）、11q22 - q25（2例）、17p13（2例）频繁出现缺失，以及整条X染色体缺失（2例）。在大多数染色体中观察到DNA扩增。5例在1p32 - pter区域显示DNA增加。在6p、11q、12q、17q、19p、20q和Xp染色体中也频繁发现DNA增加（各3例）。有趣的是，DNA增加在鼻腔/鼻型NK细胞淋巴瘤中比在NK细胞淋巴瘤/白血病中更频繁。这些基因改变与部分病例中发现的核型特征密切相关。6q和13q频繁的DNA缺失表明这些区域肿瘤抑制基因的存在对NK细胞转化很重要。除了在这些罕见的NK细胞恶性肿瘤中建立新的基因组失衡模式（这可能是未来分子分析的靶点）外，本研究还提供了关于NK细胞淋巴瘤基因改变的重要信息，这可能有助于确定它们在当前淋巴瘤分类方案中的位置，而当前的分类方案越来越注重表型和基因型的相关性。
