title: Amplification of the insulin-like growth factor 1 receptor gene is a rare event in adrenocortical adenocarcinomas: searching for potential mechanisms of overexpression.
abstract: BACKGROUND
  IGF1R overexpression appears to be a prognostic biomarker of metastatic pediatric adrenocortical tumors. However, the molecular mechanisms that are implicated in its upregulation remain unknown. Aim. To investigate the potential mechanisms involved in IGF1R overexpression.
  
  
  METHODS
  We studied 64 adrenocortical tumors. IGF1R copy number variation was determined in all patients using MLPA and confirmed using real time PCR. In a subgroup of 32 patients, automatic sequencing was used to identify IGF1R allelic variants and the expression of microRNAs involved in IGF1R regulation by real time PCR.
  
  
  RESULTS
  IGF1R amplification was detected in an adrenocortical carcinoma that was diagnosed in a 46-year-old woman with Cushing's syndrome and virilization. IGF1R overexpression was demonstrated in this case. In addition, gene amplification of other loci was identified in this adrenocortical malignant tumor, but no IGF1R copy number variation was evidenced in the remaining cases. Automatic sequencing revealed three known polymorphisms but they did not correlate with its expression. Expression of miR-100, miR-145, miR-375, and miR-126 did not correlate with IGF1R expression.
  
  
  CONCLUSIONS
  We demonstrated amplification and overexpression of IGF1R gene in only one adrenocortical carcinoma, suggesting that these combined events are uncommon. In addition, IGF1R polymorphisms and abnormal microRNA expression did not correlate with IGF1R upregulation in adrenocortical tumors.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Brazil.
authors.forename: Tamaya Castro
authors.initials: TC
authors.lastname: Ribeiro
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Brazil ; Unidade de Endocrinologia Genética/LIM25, Brazil.
authors.forename: Alexander Augusto
authors.initials: AA
authors.lastname: Jorge
authors.affiliation: Unidade de Suprarrenal, Disciplina de Endocrinologia e Metabologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Madson Q
authors.initials: MQ
authors.lastname: Almeida
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Brazil.
authors.forename: Beatriz Marinho de Paula
authors.initials: BM
authors.lastname: Mariani
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Brazil.
authors.forename: Mirian Yumi
authors.initials: MY
authors.lastname: Nishi
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Brazil.
authors.forename: Berenice Bilharinho
authors.initials: BB
authors.lastname: Mendonca
authors.affiliation: Unidade de Suprarrenal, Disciplina de Endocrinologia e Metabologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Maria Candida Barisson Villares
authors.initials: MC
authors.lastname: Fragoso
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Brazil.
authors.forename: Ana Claudia
authors.identifier: 0000-0001-6782-693X
authors.initials: AC
authors.lastname: Latronico
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D017526:Receptor, IGF Type 1
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