双生子调查、系谱分析、遗传流行病学和染色体分析都已证实肿 瘤的发生具有明显的遗传基础,它们有的呈单基因遗传;有的呈多基 因遗传;有的与染色体畸变有关,有的构成了遗传综合征的一部分。 Etiology cancer as late as the 1970s human cancers remained a black box. Theories were abundant: Cancer was hypothesized to result from defective immunity viruses, dysregulated differentiation mutations... In the absence of hard evidence to confirm or refute any of these theories it was difficult to be optimistic that cancer would soon be understood, or that there was much hope for patients afflicted with disease. This has changed dramatically as a result of revolution in cancer research that has occurred in the last decade. If this revolution were to be summarized in a single sentence, that sentence would be"Cancer is, in essence, a genetic disease. Although cancer is complex, and environmental and other nongenetic factors clearly p lay a role in many stages of the neoplastic process, the tremendous progress made in understanding tumorigenesis in large part is owing to the discovery of the genes, that when mutated, lead to cancer 单基因遗传的肿瘤 人类单基因遗传的肿瘤种类虽然不少,但在全部人类肿瘤中所占 的比例不大。其中较为多见的有视网膜母细胞瘤、肾母细胞瘤、神经 母细胞瘤、皮肤鳞癌、嗜铬细胞瘤、多发性神经纤维瘤等。视网膜母 细胞瘤是一种眼部的肿瘤,每20000个活婴中即有1个罹患此病,呈 常染色体显性(AD)遗传,发病年龄较早(常在4岁以内),多累及 双眼。此外,在人群中还有一种视网膜母细胞瘤呈散发状态,发病年 龄较晚,且多为单侧性,与遗传的关系不大(图16-1)。总之,单基2 双生子调查、系谱分析、遗传流行病学和染色体分析都已证实肿 瘤的发生具有明显的遗传基础，它们有的呈单基因遗传；有的呈多基 因遗传；有的与染色体畸变有关，有的构成了遗传综合征的一部分。 Etiology of Cancer As late as the 1970s,human cancers remained a black box. Theories were abundant: Cancer was hypothesized to result from defective immunity, viruses, dysregulated differentiation, mutations……In the absence of hard evidence to confirm or refute any of these theories, it was difficult to be optimistic that cancer would soon be understood, or that there was much hope for patients afflicted with disease. This has changed dramatically as a result of revolution in cancer research that has occurred in the last decade. If this revolution were to be summarized in a single sentence, that sentence would be “Cancer is, in essence, a genetic disease.” Although cancer is complex, and environmental and other nongenetic factors clearly play a role in many stages of the neoplastic process, the tremendous progress made in understanding tumorigenesis in large part is owing to the discovery of the genes, that when mutated, lead to cancer. 一、单基因遗传的肿瘤 人类单基因遗传的肿瘤种类虽然不少，但在全部人类肿瘤中所占 的比例不大。其中较为多见的有视网膜母细胞瘤、肾母细胞瘤、神经 母细胞瘤、皮肤鳞癌、嗜铬细胞瘤、多发性神经纤维瘤等。视网膜母 细胞瘤是一种眼部的肿瘤，每 20000 个活婴中即有 1 个罹患此病，呈 常染色体显性（AD）遗传，发病年龄较早（常在 4 岁以内），多累及 双眼。此外，在人群中还有一种视网膜母细胞瘤呈散发状态，发病年 龄较晚，且多为单侧性，与遗传的关系不大（图 16-1）。总之，单基