Ishak Geraldo, Leal Mariana Ferreira, Dos Santos Ney Pereira Carneiro, Demachki Samia, Nunes Caroline Aquino Moreira, do Nascimento Borges Barbara, Calcagno Danielle Queiroz, Smith Marília Cardoso, Assumpção Paulo Pimentel, Burbano Rommel Rodríguez
Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, 60673-000, Brazil.
Clin Exp Med. 2015 Aug;15(3):421-6. doi: 10.1007/s10238-014-0311-8. Epub 2014 Sep 9.
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.
胆囊癌是一种罕见的恶性肿瘤，预后较差。MYC和p53与胆囊癌发生有关。然而，关于它们在这种肿瘤中调控的分子机制知之甚少。在此，我们评估了胆囊肿瘤中MYC和TP53的拷贝数及其与蛋白表达的可能关联。我们还研究了MYC是否受突变和DNA启动子甲基化的控制。在本研究中，分析了15例浸润性胆囊癌样本和6例对照样本。另一方面，MYC和p53在胆囊癌中的表达比对照样本更常见（分别为p = 0.002，p = 0.046）。在86.7%和50%的胆囊癌中分别检测到MYC和TP53基因拷贝数增加。MYC和TP53扩增与其蛋白的免疫反应性相关（分别为p = 0.029，p = 0.001）。仅在肿瘤样本中检测到MYC低甲基化，且与蛋白表达相关（p = 0.029）。在80%的肿瘤样本中检测到MYC突变。rs117856857处的G等位基因与胆囊肿瘤的存在相关（p = 0.019），并与MYC表达相关（p = 0.044）。此外，有两个肿瘤在MYC外显子2（rs28933407）出现致病突变。我们的研究强调，MYC和TP53拷贝数增加似乎是胆囊癌中的常见现象。此外，MYC的拷贝数增加、低甲基化和点突变可能导致其蛋白在这类癌症中过度表达。
