Molecular biology of lung cancer.
Molecular biology of lung cancer.
复制标题
DOI：
10.1016/s0959-8049(01)80008-3
复制
发表时间：
2001-10
影响因子：
8.4
通讯作者：
G. Sozzi
中科院分区：
文献类型：
--
作者：
G. Sozzi
已经确定肺癌的发生是多种体细胞遗传变化（lo-20突变）积累的结果，涉及关键基因，其蛋白质产物控制细胞增殖、分化和凋亡。这些基因包括原癌基因（正生长调节剂）、肿瘤抑制基因（负生长调节剂）和参与细胞凋亡控制的基因。此外，其他更普遍的变化是染色体重排，如缺失和非互反易位，微卫星（DNA重复序列）不稳定，端粒酶表达失控和血管生成（图1）。在临床表现明显的肺癌出现之前，由于支气管上皮长期暴露于致癌物，支气管上皮可发生一系列形态学上明显的癌前变化，如增生、不典型增生和原位癌，这种现象称为“野癌效应”。肿瘤前细胞可能包含一些与肺癌细胞相同的分子遗传异常（图1）。识别正常和癌前支气管组织有恶性进展危险的危险因素因此可以在分子水平上定义。识别和描述驱动肺癌发展和进展的基因变化可以为我们提供各种分子标记，这些分子标记可能最终重新定义癌症诊断的标准，并通过应用敏感技术检测可获得的生物标本中的分子变化，以及开发新的靶向癌症和癌症前治疗方法，为早期检测提供新的工具。
It has been established that lung cancer arises as a consequence of the accumulation of multiple somatic genetic changes (lo-20 mutations) involving critical genes whose protein products control cell proliferation, differentiation and apoptosis. These genes include protooncogene(positive growth regulators), tumour suppressor genes (negative growth regulators) and genes involved in apoptotic control. In addition, other more generalised changes are chromosomal rearrangements such as deletions and non-reciprocal translocation, microsatellites(DNA repeat sequences) instability, deregulated expression of telomerase and angiogenesis (Fig. 1). Before the appearance of a clinically overt lung cancer, a series of morphologically distinct preneoplastic changes such as hyperplasia, dysplasia and carcinoma in situ can occur in the bronchial epithelium, as a result of the chronic exposure of the bronchial epithelium to carcinogens, a phenomenon termed ‘field cancerization effect’. The preneoplastic cell may contain several molecular genetic abnormalities identical to those observed in lung cancer cells (Fig. 1). Risk factors that identify normal and premalignant bronchial tissue at risk for malignant progression can thus be defined at a molecular level. Identification and characterisation of the genetic changes that drive lung cancer development and progression can provide us with a variety of molecular markers that may ultimately redefine the criteria for cancer diagnosis and provide new tools for early detection, through the application of sensitive techniques that detect molecular changes in accessible biological specimens and for developing novel targeted cancer and pre-cancer therapies.