Involvement of adenomatous polyposis coli (APC) gene in testicular yolk sac tumor of infants
Involvement of adenomatous polyposis coli (APC) gene in testicular yolk sac tumor of infants
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DOI：
10.1016/j.humpath.2005.09.008
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Motoyama, T
中科院分区：
文献类型：
--
作者：
Kato, N;Shibuya, H;Motoyama, T
婴儿睾丸卵黄囊瘤（YST）的发病机制尚不清楚。婴儿 YST 很少显示同染色体 12p 或非整倍性，而这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抑癌基因的参与，包括腺瘤性结肠息肉病（APC）基因。在本研究中，我们检测了10个婴儿纯YST的APC基因突变、等位基因丢失、启动子甲基化和蛋白表达状态，以评估APC基因是否在婴儿YST的发病机制中发挥重要作用。在所检查的 9 个 YST 中，至少有 3 个 (30%) 检测到 APC 基因定位的 5q21 杂合性丢失。 10 个 YST 均未显示突变。在 10 个 YST 中的 7 个（70%）中检测到启动子甲基化；在 7 个显示甲基化的 YST 中，有 3 个 YST 在 5q21 处也存在杂合性丢失。免疫组织化学显示，8个婴儿YST不表达APC蛋白，而2个未显示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，等位基因丢失和/或启动子甲基化导致的 APC 基因失活与婴儿 YST 的发生有关。 (c) 2006 Elsevier Inc. 保留所有权利。
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. (c) 2006 Elsevier Inc. All rights reserved.