Kratzke R A, Shimizu E, Kaye F J
Cancer Treat Res. 1992;63:61-85. doi: 10.1007/978-1-4615-3088-6_3.
The rapid pace of research in the genetics of human cancer will predictably render any review of the topic out of date by the time of its publication. Prospects for the near future will likely include the identification of a chromosome 3p gene(s) linked with the development of familial renal cancer and, perhaps, also lung cancer. In addition, the availability from the Human Genome Project of an increasing number of well-characterized markers will accelerate the search for additional human recessive oncogenes. Many questions still remain about the etiology of lung cancer and how to apply this information for patient care. For example, identification of the cell of origin for small cell and non-small cell lung cancers will facilitate our understanding of the development of these tumors and improve the possibilities for future preventive strategies. In addition, we now realize that these cancers arise from the sequential accumulation of multiple genetic mutations (Table 3; Fig. 1). Therefore, a central question is which of these targets are essential for the process of carcinogenesis, and whether there is a critical temporal order for this process with a defined premalignant phase in a discrete field of bronchial tissue. In addition, are there genetically inherited susceptibilities to the development of lung cancer (either directly or via variabilities in carcinogen metabolism) that could be accurately identified in the general population? Finally, is there a rate-limiting mutation and will the genetic correction of this defect suffice to restore growth regulation, or will the replacement of multiple gene products be required for tumor suppression? We are already witnessing the beginnings of the use of molecular diagnostic markers as a research tool for assigning prognostic information. The expression of neuroendocrine markers in non-small cell lung cancer has recently been applied as an indicator of the potential response to combination chemotherapy [15]. Similar methods are being applied to the expression of tumor suppressor genes or the presence of somatic mutations in dominant oncogenes such as the ras gene. However, the clinical benefit of this prognostic information with currently available treatment programs is still uncertain.(ABSTRACT TRUNCATED AT 400 WORDS)
人类癌症遗传学研究的快速发展，不出所料地会使任何关于该主题的综述在发表时就过时。近期的前景可能包括鉴定与家族性肾癌以及或许还有肺癌发生相关的3号染色体p基因。此外，人类基因组计划提供的特征明确的标记物越来越多，这将加速寻找其他人类隐性癌基因。关于肺癌的病因以及如何将这些信息应用于患者护理，仍有许多问题。例如，确定小细胞肺癌和非小细胞肺癌的起源细胞将有助于我们理解这些肿瘤的发生，并增加未来预防策略的可能性。此外，我们现在认识到这些癌症是由多个基因突变的相继积累引起的（表3；图1）。因此，一个核心问题是这些靶点中哪些对致癌过程至关重要，以及这个过程是否有一个关键的时间顺序，在支气管组织的一个离散区域有一个明确的癌前阶段。此外，在普通人群中是否存在可准确识别的肺癌发生的遗传易感性（直接或通过致癌物代谢的变异性）？最后，是否存在限速突变，对该缺陷的基因校正是否足以恢复生长调节，还是需要替换多个基因产物来抑制肿瘤？我们已经目睹了分子诊断标记物开始被用作分配预后信息的研究工具。非小细胞肺癌中神经内分泌标记物的表达最近已被用作联合化疗潜在反应的指标[15]。类似的方法也应用于肿瘤抑制基因的表达或显性癌基因如ras基因中体细胞突变的存在。然而，目前可用治疗方案中这种预后信息的临床益处仍不确定。（摘要截短至400字）
