Sawyer J R, Swanson C M, Koller M A, North P E, Ross S W
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, USA.
Cancer. 1995 Oct 1;76(7):1238-44. doi: 10.1002/1097-0142(19951001)76:7<1238::aid-cncr2820760722>3.0.co;2-8.
Acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas are associated with the B-cell chromosomal translocation t(8;14)(q24; q32). The most common secondary chromosome aberrations in these patients involve 1q and are believed to be associated with tumor progression. A mechanism for the origin of these 1q aberrations has not been demonstrated. To their knowledge, the authors report the first human immunodeficiency virus (HIV)-positive patient to have centromeric decondensation and multibranched chromosome aberrations of chromosomes 1 and 16 resulting in telomeric associations and "jumping translocations" of 1q.
Tumor cells from peritoneal fluid of an HIV-positive patient were cultured for 24, 48, and 72 hours and analyzed by both conventional G-banding and fluorescence in situ hybridization.
G-band analysis showed a stemline with t(8;14)(q24;q32), but also showed the progression from centromeric decondensation to multibranched chromosome configurations of chromosomes 1 and 16. The interchange and duplications of chromosome arms resulted in the gain of extra copies of 1q material on a number of different chromosomes, but also the loss of 16q in at least one sideline and the formation of micronuclei. Fluorescence in situ hybridization analysis demonstrated that micronuclei predominantly involved chromosome 1 and, to a lesser extent, chromosome 16.
The cytogenetic findings in this unique case suggest that immunodeficiency may be a factor involved in centromeric instability, multibranching, and the progression to the subsequent formation of telomeric fusions and multiple unbalanced translocations of 1q (jumping translocations). The striking similarity of the centromeric instability in this patient to those with ICF syndrome (variable immunodeficiency, centromeric heterochromatin instability, and facial anomalies) suggests hypomethylation as the etiologic mechanism for the chromosome instability.
获得性免疫缺陷综合征相关的非霍奇金淋巴瘤与B细胞染色体易位t(8;14)(q24;q32)相关。这些患者中最常见的继发性染色体畸变涉及1q，并且被认为与肿瘤进展有关。这些1q畸变的起源机制尚未得到证实。据作者所知，他们报告了首例人类免疫缺陷病毒（HIV）阳性患者出现1号和16号染色体着丝粒解聚和多分支染色体畸变，导致1q的端粒关联和“跳跃式易位”。
对一名HIV阳性患者腹腔积液中的肿瘤细胞进行培养2４、48和72小时，并通过传统的G显带和荧光原位杂交进行分析。
G显带分析显示一条具有t(8;14)(q24;q32)的干系，但也显示了从着丝粒解聚到1号和16号染色体多分支染色体构型的进展。染色体臂的互换和重复导致在许多不同染色体上获得额外的1q物质拷贝，但至少一条旁系中也出现16q缺失和微核形成。荧光原位杂交分析表明，微核主要涉及1号染色体，其次是16号染色体。
这一独特病例的细胞遗传学发现表明，免疫缺陷可能是着丝粒不稳定、多分支以及随后进展为端粒融合和1q多次不平衡易位（跳跃式易位）形成的一个因素。该患者着丝粒不稳定与ICF综合征（可变免疫缺陷、着丝粒异染色质不稳定和面部异常）患者的着丝粒不稳定惊人相似，提示低甲基化是染色体不稳定的病因机制。
