title: CTNNB1 gene mutations, pituitary transcription factors, and MicroRNA expression involvement in the pathogenesis of adamantinomatous craniopharyngiomas.
abstract: Genes involved in formation/development of the adenohypophysis, CTNNB1 gene, and microRNAs might be implicated in the craniopharyngioma pathogenesis. The objective of this study is to perform the molecular analysis of HESX1, PROP1, POU1F1, and CTNNB1 genes and evaluate a panel of miRNA expression in craniopharyngioma. We also verified whether the presence of CTNNB1 mutation is associated with clinical findings and miRNA expression. The study included 16 patients with adamantinomatous craniopharyngioma (nine children and seven adults; eight females and eight males; 6-55 years, median 15.5 years). DNA, RNA, and cDNA were obtained from craniopharyngioma and normal pituitaries. DNA was also extracted from peripheral blood of healthy subjects. All genes were amplified by polymerase chain reaction and direct sequenced. Relative quantification of miRNA expression was calculated using the 2(-ΔΔCt) method. We found no mutations in HESX1, PROP1, and POU1F1 genes and four polymorphisms in PROP1 gene which were in Hardy-Weinberg equilibrium and had similar allelic frequencies in craniopharyngioma and controls. We found seven different mutations in CTNNB1 in eight of 16 patients. Younger patients presented more frequently CTNNB1 mutation than adults. We observed hyperexpression of miR-150 (1.7-fold); no different expression of miR-16-1, miR-21, and miR23a; and an underexpression of miR-141, let-7a, miR-16, miR-449, miR-145, miR-143, miR-23b, miR-15a, and miR-24-2 (ranging from -7.5 to -2.5-fold; p = 0.02) in craniopharyngioma. There was no association between tumor size or the recurrence and the presence of CTNNB1mutations. miR-16 and miR-141 were underexpressed in craniopharyngioma presenting CTNNB1 mutations. miR-23a and miR24-2 were hyperexpressed in patients who underwent only one surgery. Mutations or polymorphisms in pituitary transcription factors are unlikely to contribute to the adamantinomatous craniopharyngioma pathogenesis, differently of CTNNB1 mutations. Our data suggest the potential involvement of the deregulation of miRNA expression in the craniopharyngioma pathogenesis and outcome and also that the miRNA could modulate the Wnt signaling pathway in craniopharyngioma tumorigenesis.
authors.affiliation: Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil.
authors.forename: Marina Lanciotti
authors.initials: ML
authors.lastname: Campanini
authors.forename: Leandro Machado
authors.initials: LM
authors.lastname: Colli
authors.forename: Beatriz Maria Carvalho
authors.initials: BM
authors.lastname: Paixao
authors.forename: Tatiana Pereira Freitas
authors.initials: TP
authors.lastname: Cabral
authors.forename: Fernando Colbari
authors.initials: FC
authors.lastname: Amaral
authors.forename: Helio Rubens
authors.initials: HR
authors.lastname: Machado
authors.forename: Luciano Serafin
authors.initials: LS
authors.lastname: Neder
authors.forename: Fabiano
authors.initials: F
authors.lastname: Saggioro
authors.forename: Ayrton Custodio
authors.initials: AC
authors.lastname: Moreira
authors.forename: Sonir Roberto Rauber
authors.initials: SR
authors.lastname: Antonini
authors.forename: Margaret
authors.initials: M
authors.lastname: de Castro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003397:Craniopharyngioma / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D050817:Transcription Factor Pit-1 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; C489736:HESX1 protein, human; D018398:Homeodomain Proteins; D035683:MicroRNAs; C494187:POU1F1 protein, human; C102134:Prophet of Pit-1 protein; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D051176:beta Catenin