睾丸生殖细胞肿瘤的发病机制。

L H Looijenga, J W Oosterhuis
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引用次数: 194

摘要

人类生殖细胞肿瘤包括不同种类的肿瘤。在睾丸中,有三种不同的实体:婴儿睾丸的畸胎瘤-卵黄囊肿瘤,青少年和成人的精原细胞瘤和非精原细胞瘤,以及精原细胞瘤。对这些肿瘤的流行病学、组织学、临床行为和染色体构成的研究支持了源自生殖细胞的不同实体的概念,但每个实体都有不同的发病机制。婴儿睾丸的畸胎瘤要么没有染色体畸变,要么表现出(部分)染色体的过度或不足的模式,如在婴儿睾丸的卵黄囊肿瘤中检测到的那样。相比之下,精原细胞瘤和非精原细胞瘤显示出一致的损失和获得模式,即染色体分别为11、13和18、7、8和X,这与婴儿睾丸畸胎瘤和卵黄囊肿瘤中的发现不同。最一致的染色体结构异常是同工染色体12p。缺乏i(12p)的肿瘤存在12p的其他结构异常,其中12p11.2-p12.1扩增。12p11.2-p12.1的病理相关基因可能位于约1.7 mb的片段上。12p序列的增加可能与侵袭性生长有关。9号染色体的增加是精原细胞瘤唯一一致的染色体异常。婴儿畸胎瘤和精原细胞瘤是良性肿瘤。婴儿卵黄囊瘤是一种恶性生殖细胞瘤。精原细胞瘤和非精原细胞瘤是恶性的,是年轻白人男性最常见的癌症。精原细胞瘤和非精原细胞瘤的放化疗治愈率超过90%,高于成人其他实体癌。此外,这些肿瘤的前驱病变可以很容易地治疗,证明了开发早期诊断手段的努力是合理的。最后,讨论了精原细胞瘤和非精原细胞瘤的发病关系,以及三种类型睾丸生殖细胞瘤的动物模型。
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Pathogenesis of testicular germ cell tumours.

Human germ cell tumours comprise a heterogeneous group of neoplasms. In the testis, three entities are distinguished, the teratomas-yolk sac tumours of the infantile testis, the seminomas and nonseminomas of adolescents and adults, and the spermatocytic seminomas. Studies on epidemiology, histology, clinical behaviour, and chromosomal constitution of these tumours support the concept of distinct entities derived from germ cells but each with a different pathogenesis. Either the teratomas of the infantile testis show no chromosomal aberrations, or display a pattern of over- and under-representation of (parts of) chromosomes as detected in the yolk sac tumours of the infantile testis. In contrast, the seminomas and nonseminomas reveal a consistent pattern of losses and gains, that is, chromosomes 11, 13 and 18, and 7, 8 and X, respectively, that is different from that found in the infantile testis teratomas and yolk sac tumours. The most consistent structural chromosomal abnormality is an isochromosome 12p. Tumours lacking i(12p) have other structural abnormalities of 12p, among them amplification of 12p11.2-p12.1. The pathogenetically relevant genes on 12p11.2-p12.1 are probably on a fragment of about 1.7 mb. Gain of 12p sequences may be related to invasive growth. Gain of chromosome 9 is the only consistent chromosomal anomaly of spermatocytic seminomas. Infantile teratomas and spermatocytic seminomas are benign tumours. Infantile yolk sac tumour is a malignant germ cell tumour. Seminomas and nonseminomas are malignant, and the most common cancer in young Caucasian males. The cure rate of seminomas and non-seminomas with radio- and chemotherapy is over 90%, which is higher than that of any other solid cancer in adults. In addition, the precursor lesions of these tumours can be treated readily, justifying efforts to develop means for early diagnosis. Finally, the pathogenetic relationship between seminomas and nonseminomas, and the available animal models for the three groups of testicular germ cell tumours are discussed.

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