Stark Batia, Jeison Marta, Glaser-Gabay Leticia, Bar-Am Irit, Mardoukh Jacques, Ash Shifra, Atias Dina, Stein Jerry, Zaizov Rina, Yaniv Isaac
Schneider Children's Medical Center of Israel, Tel Aviv University, Tel Aviv, Israel.
Cancer Lett. 2003 Jul 18;197(1-2):75-9. doi: 10.1016/s0304-3835(03)00083-1.
Conventional cytogenetic, molecular cytogenic and genetic methods disclosed a broad spectrum of genetic abnormalities leading to gain and loss of chromosomal segments in advanced stage neuroblastoma (NBL). Specific correlation between the genetic findings could delineate distinct genetic pathways, of which the biology and prognostic significance is as yet undetermined. Using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) on metaphases from 16 patients with advanced stage NBL, it was possible to explore the whole spectrum of rearrangement within complex karyotypes and to detect hidden recurrent translocations. All translocations were unbalanced. The most prevalent recurrent unbalanced translocations resulted in 17q gain in 12 patients (75%), 11q loss in nine patients (56%), and 1p deletion/imbalance in eight patients (50%). The most frequent recurrent translocation was der(11)t(11;17) in six patients. Three cytogenetic pathways could be delineated. The first, with six patients, was characterized by the unbalanced translocation der(11)t(11;17), detected only by SKY, resulting in the concomitant 17q gain and 11q loss. No MYCN amplification or 1p deletion (except one patient with 1p imbalance) were found, while 3p deletion, and complex karyotypes were common. The second subgroup, with four patients, had 17q gain and 1p deletion, and in two patients 11q loss, that was apparent only by FISH. 1p deletion occurred through der(1)t(1;17) or del(1p). The third subgroup of four patients was characterized by MYCN amplification with 17q gain and 1p deletion, very rarely with 11q loss (one patient) through a translocation with a non-17q partner. The SKY subclassifications were in accordance with the findings reported by molecular genetic techniques, and may indicate that distinct oncogenes and suppressor genes are involved in the der(11)t(11;17) pathway of advanced stage NBL.
传统的细胞遗传学、分子细胞遗传学和遗传学方法揭示了晚期神经母细胞瘤（NBL）中导致染色体片段增减的广泛遗传异常。遗传研究结果之间的特定关联可以勾勒出不同的遗传途径，但其生物学特性和预后意义尚未明确。通过对16例晚期NBL患者的中期细胞进行光谱核型分析（SKY）和荧光原位杂交（FISH），得以探究复杂核型内重排的全貌，并检测出隐匿的复发性易位。所有易位均为不平衡易位。最常见的复发性不平衡易位导致12例患者（75%）出现17q增益、9例患者（56%）出现11q缺失以及8例患者（50%）出现1p缺失/不平衡。最常见的复发性易位是6例患者中的der(11)t(11;17)。可以勾勒出三种细胞遗传学途径。第一种途径有6例患者，其特征是不平衡易位der(11)t(11;17)，仅通过SKY检测到，导致同时出现17q增益和11q缺失。未发现MYCN扩增或1p缺失（除1例有1p不平衡的患者外），而3p缺失和复杂核型较为常见。第二个亚组有4例患者，有17q增益和1p缺失，2例患者有11q缺失，仅通过FISH才能明显看出。1p缺失通过der(1)t(1;17)或del(1p)发生。第三个亚组的4例患者的特征是MYCN扩增伴17q增益和1p缺失，通过与非17q伙伴的易位导致11q缺失的情况非常罕见（1例患者）。SKY亚分类与分子遗传学技术报告的结果一致，可能表明不同的癌基因和抑癌基因参与了晚期NBL的der(11)t(11;17)途径。
