title: Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas.
abstract: Gallbladder cancer is a rare malignancy and presents a poor prognosis. MYC and p53 have been implicated in gallbladder carcinogenesis. However, little is known about the molecular mechanisms involved in their regulation in this neoplasia. Here, we evaluated the MYC and TP53 copy numbers in gallbladder tumors and their possible association with protein expression. We also investigated whether MYC may be controlled by mutations and DNA promoter methylation. In the present study, 15 samples of invasive gallbladder carcinomas and six control samples were analyzed. On the other hand, the expression of MYC and p53 was more frequent in gallbladder carcinomas than in control samples (p = 0.002, p = 0.046, respectively). Gain of copies of the MYC and TP53 genes was detected in 86.7 and 50 % of gallbladder carcinomas, respectively. MYC and TP53 amplifications were associated with immunoreactivity of their protein (p = 0.029, p = 0.001, respectively). MYC hypomethylation was only detected in tumoral samples and was associated with its protein expression (p = 0.029). MYC mutations were detected in 80 % of tumor samples. The G allele at rs117856857 was associated with the presence of gallbladder tumors (p = 0.019) and with MYC expression (p = 0.044). Moreover, two tumors presented a pathogenic mutation in MYC exon 2 (rs28933407). Our study highlights that the gain of MYC and TP53 copies seems to be a frequent finding in gallbladder cancer. In addition, gain of copies, hypomethylation and point mutations at MYC may contribute to overexpression of its protein in this type of cancer.
authors.affiliation: Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, 60673-000, Brazil.
authors.forename: Geraldo
authors.initials: G
authors.lastname: Ishak
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.forename: Ney Pereira Carneiro
authors.initials: NP
authors.lastname: Dos Santos
authors.forename: Samia
authors.initials: S
authors.lastname: Demachki
authors.forename: Caroline Aquino Moreira
authors.initials: CA
authors.lastname: Nunes
authors.forename: Barbara
authors.initials: B
authors.lastname: do Nascimento Borges
authors.forename: Danielle Queiroz
authors.initials: DQ
authors.lastname: Calcagno
authors.forename: Marília Cardoso
authors.initials: MC
authors.lastname: Smith
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.forename: Rommel Rodríguez
authors.initials: RR
authors.lastname: Burbano
mesh_terms: D002277:Carcinoma / Q000473:pathology*; D044127:Epigenesis, Genetic; D005260:Female; D005706:Gallbladder Neoplasms / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53