title: High frequency of loss of heterozygosity at 11p15 and IGF2 overexpression are not related to clinical outcome in childhood adrenocortical tumors positive for the R337H TP53 mutation.
abstract: A germline TP53 R337H mutation is present in childhood adrenocortical tumors (ACT) from southern Brazil. Other genetic alterations are also frequently found in these tumors. This study was designed to assess whether alterations of the 11p15 region exist in childhood ACT, accounting for IGF2 overexpression in these tumors, and how they are related to clinical outcome. Tumor DNA of 12 children with ACT (4 adenomas and 8 carcinomas) and from the blood of their parents was analyzed. All patients showed 11p15 loss of heterozygosity (LOH) in the tumor. In contrast to the single case of paternal LOH, IGF2 was overexpressed in tumors with maternal allele loss. Our data show that 11p15 LOH is a widespread finding in childhood ACT not related with malignancy, contrary to adult ACT. Alterations in the expression of other genes in the same region (e.g., CDKN1C) may contribute to ACT tumorigenesis.
authors.affiliation: Instituto de Pesquisa Pelé Pequeno Principe, Curitiba, Av. Silva Jardim, Paraná, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosati
authors.forename: Flavia
authors.initials: F
authors.lastname: Cerrato
authors.forename: Mabrouka
authors.initials: M
authors.lastname: Doghman
authors.forename: Mara A D
authors.initials: MA
authors.lastname: Pianovski
authors.forename: Guilherme A
authors.initials: GA
authors.lastname: Parise
authors.forename: Gislaine
authors.initials: G
authors.lastname: Custódio
authors.forename: Gerard P
authors.initials: GP
authors.lastname: Zambetti
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Andrea
authors.initials: A
authors.lastname: Riccio
authors.forename: Bonald C
authors.initials: BC
authors.lastname: Figueiredo
authors.forename: Enzo
authors.initials: E
authors.lastname: Lalli
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D000367:Age Factors; D019943:Amino Acid Substitution; D001938:Brazil / Q000453:epidemiology; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D018392:Genomic Imprinting; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics*; D019656:Loss of Heterozygosity; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D017354:Point Mutation; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins; D007335:Insulin-Like Growth Factor II
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