Gehring M, Berthold F, Edler L, Schwab M, Amler L C
Department of Cytogenetics, German Cancer Research Center, Heidelberg, Germany.
Cancer Res. 1995 Nov 15;55(22):5366-9.
Human neuroblastoma cells often have deletions of the distal short arm of chromosome 1 (1p). Earlier studies using chromosome analysis had suggested that the 1p deletion is correlated with a poor survival chance for the patient. We have reevaluated this possibility by analyzing 51 neuroblastomas for loss of heterozygosity (LOH) at 1p. We detected LOH in 32% of the cases. LOH did not correlate with the age of the patients at diagnosis or with tumor stage but was correlated significantly with amplification of the MYCN proto-oncogene. Nine of 10 MYCN-amplified tumors had deletions in 1p (P < 0.001). Survival chances of patients with tumors carrying MYCN amplification together with the deletion at 1p were decreased significantly (eight of nine affected patients died) compared with a patient group without any of these aberrations (P < 0.001). However, the deletion of 1p alone without MYCN amplification was not associated with a poor outcome compared with patients who had neither deletion nor amplification (only two of eight affected patients died; P = 0.803). From these data we conclude that 1p deletions are not reliable markers to determine a patient's prognosis. They may, however, identify a subgroup of neuroblastomas in which MYCN is amplified readily, resulting in rapid tumor progression.
人类神经母细胞瘤细胞常常出现1号染色体(1p)短臂远端的缺失。早期使用染色体分析的研究表明,1p缺失与患者较差的生存几率相关。我们通过分析51例神经母细胞瘤1p杂合性缺失(LOH)情况,重新评估了这种可能性。我们在32%的病例中检测到了LOH。LOH与诊断时患者的年龄或肿瘤分期无关,但与MYCN原癌基因的扩增显著相关。10例MYCN扩增的肿瘤中有9例存在1p缺失(P < 0.001)。与没有任何这些异常的患者组相比,携带MYCN扩增并伴有1p缺失的肿瘤患者的生存几率显著降低(9例受影响患者中有8例死亡)(P < 0.001)。然而,与既无缺失也无扩增的患者相比,仅1p缺失而无MYCN扩增与不良预后无关(8例受影响患者中只有2例死亡;P = 0.803)。从这些数据我们得出结论,1p缺失不是确定患者预后的可靠标志物。然而,它们可能识别出一个神经母细胞瘤亚组,其中MYCN容易扩增,导致肿瘤快速进展。