Thomas G
Laboratoire de Génétique des Tumeurs, Institut Curie, Paris, France.
Pathol Biol (Paris). 1995 Mar;43(3):143-9.
In spite of early observations indicating an association of cancer with genomic alterations, the precise knowledge of the causal mutations was only initiated since the last 20 years when the techniques of molecular genetics were applied to observations obtained by investigators working in the field of retrovirology, cell biology, cytogenetics and human genetics. A large number of genes which are recurrently altered in defined tumor types has been identified. Schematically it is possible to distinguish dominant mutations which lead to the oncogenic conversion of proto-oncogenes and recessive mutations of antioncogenes which require for phenotypic expression the inactivation of the second allele. Activation of protooncogenes and inactivation of antioncogenes cooperate within the same cells to the determination of the tumor phenotype. Inherited alterations causing major predisposition to tumor development involve most frequently antioncogenes. Most proto-oncogenes and major tumor susceptibility genes are now known. However, we have a poor understanding of the pathologic mechanism triggered by their mutations.
尽管早期观察表明癌症与基因组改变有关，但直到最近20年，当分子遗传学技术应用于逆转录病毒学、细胞生物学、细胞遗传学和人类遗传学领域研究人员所获得的观察结果时，才开始对致癌突变有了精确的认识。已经确定了大量在特定肿瘤类型中反复发生改变的基因。从理论上讲，可以区分导致原癌基因致癌转化的显性突变和抗癌基因的隐性突变，后者的表型表达需要第二个等位基因失活。原癌基因的激活和抗癌基因的失活在同一细胞内共同作用以决定肿瘤表型。导致肿瘤发生主要易感性的遗传改变最常涉及抗癌基因。现在大多数原癌基因和主要的肿瘤易感基因已为人所知。然而，我们对由它们的突变引发的病理机制了解甚少。
