Brodeur G M
Division of Oncology, University of Pennsylvania, Philadelphia 19104, USA.
Cancer Surv. 1995;25:67-99.
There has been considerable progress in the past decade in elucidating the molecular basis of malignant transformation of retinoblastoma, Wilms' tumour and neuroblastoma. For retinoblastoma, the story is relatively simple and the laboratory focus should be on rapid detection of germline mutations, identifying additional genetic changes associated with tumour progression and the prevention of second primary cancers, if possible. In the case of Wilms' tumour, the locus (or loci) responsible for hereditary predisposition is still unknown. Furthermore, the WT2 locus has not been cloned and there is no consistent evidence of oncogene activation. Clearly, there is still much to be done before we fully understand the genetic basis of this disease. Finally, substantial insights have been gained from the molecular analysis of neuroblastomas, but this tumour is perhaps the least well understood. Two sites of allelic loss have been identified (1p36 and 14q32), but the presumptive suppressor genes that are the targets of these changes have yet to be identified. Furthermore, it is not clear if either of these loci is responsible for a genetic predisposition to develop this tumour. Although N-myc amplification is a powerful prognostic marker of aggressive tumours, no other oncogene has been shown to be activated in tumours lacking amplification. Finally, the NGFR pathway may have an important role in regulating differentiation and programmed cell death in these cells, but other NGFR family pathways or unrelated genes may be involved as well. Hopefully, the next decade will provide us with answers to many of these open questions.
在过去十年中，在阐明视网膜母细胞瘤、肾母细胞瘤和神经母细胞瘤恶性转化的分子基础方面取得了相当大的进展。对于视网膜母细胞瘤来说，情况相对简单，实验室的重点应该是快速检测种系突变，确定与肿瘤进展相关的其他基因变化，并尽可能预防第二原发性癌症。就肾母细胞瘤而言，负责遗传易感性的基因座（或基因座）仍然未知。此外，WT2基因座尚未克隆，也没有一致的证据表明癌基因激活。显然，在我们完全了解这种疾病的遗传基础之前，还有很多工作要做。最后，通过对神经母细胞瘤的分子分析已经获得了大量见解，但这种肿瘤可能是了解最少的。已经确定了两个等位基因缺失位点（1p36和14q32），但这些变化的假定抑制基因尚未确定。此外，尚不清楚这些基因座中的任何一个是否与发生这种肿瘤的遗传易感性有关。虽然N-myc扩增是侵袭性肿瘤的一个强大预后标志物，但在缺乏扩增的肿瘤中尚未显示有其他癌基因被激活。最后，NGFR途径可能在调节这些细胞的分化和程序性细胞死亡中起重要作用，但其他NGFR家族途径或不相关的基因也可能参与其中。希望在未来十年能为我们解答许多这些悬而未决的问题。
