Peng H Q, Bailey D, Bronson D, Goss P E, Hogg D
Oncology Research Division, Toronto Hospital, Ontario.
Cancer Res. 1995 Jul 1;55(13):2871-5.
Little is known of the molecular changes that occur in germ cell tumors (GCT) of the testis. We studied three GCT cell lines and 44 tumors for loss of heterozygosity (LOH) of the tumor suppressor genes APC, MCC, DCC, RB, TP53, and WT-1. We observed that LOH occurred in 55% (21 of 38) of informative cases at DCC, in 28% (10 of 36) of informative cases at APC, in 23% (6 of 26) at MCC, in 30% (13 of 43) at RB, and in 27% (6 of 22) at WT-1. The LOH level in these tumors using anonymous primers mapping to the short and long arms of chromosome 19, which is cytogenetically normal in GCT, revealed LOH of 11 and 5%, respectively. We also observed a LOH of 22% in the TP53 gene, despite the fact that mutations in TP53 do not occur in testis cancer. Since a high frequency of LOH at DCC (18q21.3) occurs equally at all histological subsets in GCT, we conclude that the loss of the function of this gene is an early event in testicular GCTs. However, the observed LOH levels at APC/MCC (5q21), RB (13q14), and WT-1 (11p13) could represent a functional loss of the corresponding tumor suppressor gene in some GCTs or reflect the loss of sequences in the same general chromosome region but involving a different tumor suppressor locus. Therefore, detailed mapping of these chromosomes is required to define the precise locations of maximal LOH in testis cancer.
人们对睾丸生殖细胞肿瘤（GCT）中发生的分子变化了解甚少。我们研究了三种GCT细胞系和44个肿瘤，以检测肿瘤抑制基因APC、MCC、DCC、RB、TP53和WT-1的杂合性缺失（LOH）情况。我们观察到，在信息性病例中，DCC基因的LOH发生率为55%（38例中的21例），APC基因的LOH发生率为28%（36例中的10例），MCC基因的LOH发生率为23%（26例中的6例），RB基因的LOH发生率为30%（43例中的13例），WT-1基因的LOH发生率为27%（22例中的6例）。使用定位到19号染色体短臂和长臂上的匿名引物检测这些肿瘤中的LOH水平，在GCT中细胞遗传学正常的情况下，其短臂和长臂的LOH发生率分别为11%和5%。我们还观察到TP53基因的LOH发生率为22%，尽管睾丸癌中未发生TP53基因的突变。由于DCC（18q21.3）基因的高频率LOH在GCT的所有组织学亚组中均同等发生，我们得出结论，该基因功能的丧失是睾丸GCT中的早期事件。然而，在APC/MCC（5q21）、RB（13q14）和WT-1（11p13）基因处观察到的LOH水平，可能代表某些GCT中相应肿瘤抑制基因的功能丧失，或者反映同一染色体区域中序列的丢失，但涉及不同的肿瘤抑制基因座。因此，需要对这些染色体进行详细定位，以确定睾丸癌中最大LOH的精确位置。
