Kato Noriko, Shibuya Hiroyuki, Fukase Masayuki, Tamura Gen, Motoyama Teiichi
Department of Pathology, Yamagata University School of Medicine, 990-9585, Japan.
Hum Pathol. 2006 Jan;37(1):48-53. doi: 10.1016/j.humpath.2005.09.008. Epub 2005 Oct 28.
The pathogenesis of testicular yolk sac tumor (YST) of infants is still unclear. Infantile YSTs rarely show isochromosome 12p or aneuploidy, which are common in adult germ cell tumors. On the other hand, recent epigenetic studies suggest the involvement of some tumor suppressor genes, including the adenomatous polyposis coli (APC) gene. In the present study, we examined 10 infantile pure YSTs for mutation, allelic loss, promoter methylation, and protein expression status of the APC gene to evaluate whether the APC gene plays a significant role in the pathogenesis of infantile YSTs. Loss of heterozygosity at 5q21, where the APC gene is localized, was detected in at least 3 (30%) of the 9 YSTs examined. None of the 10 YSTs showed mutations. Promoter methylation was detected in 7 (70%) of the 10 YSTs; among 7 YSTs showing methylation, 3 YSTs also harbored loss of heterozygosity at 5q21. Immunohistochemically, 8 infantile YSTs did not express the APC protein, whereas 2 YSTs without showing APC methylation, as well as germ cells of normal infantile testes, expressed this protein in the cytoplasm. These data indicate that inactivation of the APC gene, by allelic loss and/or promoter methylation, is related to the occurrence of infantile YSTs.
婴儿睾丸卵黄囊瘤（YST）的发病机制仍不清楚。婴儿YST很少出现12号染色体短臂等臂染色体或非整倍体，而这些在成人生殖细胞肿瘤中很常见。另一方面，最近的表观遗传学研究表明一些肿瘤抑制基因参与其中，包括腺瘤性息肉病 coli（APC）基因。在本研究中，我们检测了10例婴儿纯YST中APC基因的突变、等位基因缺失、启动子甲基化和蛋白表达状态，以评估APC基因在婴儿YST发病机制中是否起重要作用。在所检测的9例YST中，至少有3例（30%）在APC基因所在的5q21处检测到杂合性缺失。10例YST均未显示突变。在10例YST中有7例（70%）检测到启动子甲基化；在7例显示甲基化的YST中，有3例在5q21处也存在杂合性缺失。免疫组织化学检测显示，8例婴儿YST不表达APC蛋白，而2例未显示APC甲基化的YST以及正常婴儿睾丸的生殖细胞在细胞质中表达该蛋白。这些数据表明，APC基因通过等位基因缺失和/或启动子甲基化失活与婴儿YST的发生有关。
