Peltomäki P, Lothe R, Børresen A L, Fosså S D, Brøgger A, de la Chapelle A
Department of Medical Genetics, University of Helsinki, Finland.
Int J Cancer. 1991 Feb 20;47(4):518-22. doi: 10.1002/ijc.2910470408.
Thirty-one males with testicular germ-cell tumors were studied by Southern hybridization using X- and Y-chromosome-specific probes as well as a pseudoautosomal probe. Densitometric analysis showed changes in the relative dosage of Y-chromosomal fragments in tumor DNA from 12 out of 31 patients (39%) as compared to normal DNA from the same patients. In 11 tumors the relative intensity ratios of Y-chromosome-specific fragments had decreased from the normal value of 1 to values between 0 and 0.77. An increase in the Y-chromosomal dosage was observed in 1 case. The entire Y chromosome was apparently involved in most patients but 2 tumors revealed regional variation. Tumor DNA of 2 patients with Y-chromosomal deficiency showed a concomitant increase in the X chromosomal dosage. The pseudoautosomal region that is shared by both sex chromosomes was involved in a total of 8 tumors (26%), 2 of which did not show any obvious dosage changes with probes detecting strictly X- or Y-chromosome-specific fragments. Autosomal alterations in the present tumor series have been described. A dosage change involving the sex chromosomes accompanied loss of heterozygosity at loci in 3p or 11p in 10 tumors out of 15 (67%). Seminomas tended to be affected more often than non-seminomas by either type of alteration. Our results indicate that changes in the sex chromosomes occur in a substantial proportion of male germ-cell tumors and, together with other defects, may constitute an important step in tumor development and/or progression.
利用X染色体和Y染色体特异性探针以及一个假常染色体探针，通过Southern杂交技术对31例睾丸生殖细胞肿瘤男性患者进行了研究。密度测定分析显示，与同一患者的正常DNA相比，31例患者中有12例（39%）肿瘤DNA中Y染色体片段的相对剂量发生了变化。在11个肿瘤中，Y染色体特异性片段的相对强度比从正常的1降至0至0.77之间。在1例中观察到Y染色体剂量增加。显然，大多数患者的整个Y染色体都受累，但有2个肿瘤显示出区域差异。2例Y染色体缺失患者的肿瘤DNA显示X染色体剂量同时增加。两个性染色体共有的假常染色体区域共有8个肿瘤（26%）受累，其中2个肿瘤在用检测严格X或Y染色体特异性片段的探针检测时未显示任何明显的剂量变化。本文已描述了当前肿瘤系列中的常染色体改变。在15个肿瘤中有10个（67%），涉及性染色体的剂量变化伴随着3p或11p位点杂合性的丧失。精原细胞瘤比非精原细胞瘤更容易受到这两种改变的影响。我们的结果表明，性染色体变化在相当一部分男性生殖细胞肿瘤中发生，并且与其他缺陷一起，可能构成肿瘤发生和/或进展的重要步骤。
