title: Involvement of adenomatous polyposis coli (APC) gene in testicular yolk sac tumor of infants.
abstract: 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.
authors.affiliation: Department of Pathology, Yamagata University School of Medicine, 990-9585, Japan. nkato@med.id.yamagata-u.ac.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shibuya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fukase
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018240:Endodermal Sinus Tumor / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020868:Gene Silencing; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor