Biomaterial Database

Deregulation of MYC and TP53 through genetic and epigenetic alterations in gallbladder carcinomas. 2015

Geraldo Ishak, and Mariana Ferreira Leal, and Ney Pereira Carneiro Dos Santos, and Samia Demachki, and Caroline Aquino Moreira Nunes, and Barbara do Nascimento Borges, and Danielle Queiroz Calcagno, and Marília Cardoso Smith, and Paulo Pimentel Assumpção, and Rommel Rodríguez Burbano

Núcleo de Pesquisa em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, 60673-000, Brazil.

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.

UI	MeSH Term	Description	Entries
D007150	Immunohistochemistry	Histochemical localization of immunoreactive substances using labeled antibodies as reagents.	Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297	Male		Males
D008853	Microscopy	The use of instrumentation and techniques for visualizing material and details that cannot be seen by the unaided eye. It is usually done by enlarging images, transmitted by light or electron beams, with optical or magnetic lenses that magnify the entire image field. With scanning microscopy, images are generated by collecting output from the specimen in a point-by-point fashion, on a magnified scale, as it is scanned by a narrow beam of light or electrons, a laser, a conductive probe, or a topographical probe.	Compound Microscopy,Hand-Held Microscopy,Light Microscopy,Optical Microscopy,Simple Microscopy,Hand Held Microscopy,Microscopy, Compound,Microscopy, Hand-Held,Microscopy, Light,Microscopy, Optical,Microscopy, Simple
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D002277	Carcinoma	A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for "cancer."	Carcinoma, Anaplastic,Carcinoma, Spindle-Cell,Carcinoma, Undifferentiated,Carcinomatosis,Epithelial Neoplasms, Malignant,Epithelioma,Epithelial Tumors, Malignant,Malignant Epithelial Neoplasms,Neoplasms, Malignant Epithelial,Anaplastic Carcinoma,Anaplastic Carcinomas,Carcinoma, Spindle Cell,Carcinomas,Carcinomatoses,Epithelial Neoplasm, Malignant,Epithelial Tumor, Malignant,Epitheliomas,Malignant Epithelial Neoplasm,Malignant Epithelial Tumor,Malignant Epithelial Tumors,Neoplasm, Malignant Epithelial,Spindle-Cell Carcinoma,Spindle-Cell Carcinomas,Tumor, Malignant Epithelial,Undifferentiated Carcinoma,Undifferentiated Carcinomas
D005260	Female		Females
D005706	Gallbladder Neoplasms	Tumors or cancer of the gallbladder.	Cancer of Gallbladder,Gallbladder Cancer,Cancer of the Gallbladder,Gall Bladder Cancer,Neoplasms, Gallbladder,Bladder Cancer, Gall,Bladder Cancers, Gall,Cancer, Gall Bladder,Cancer, Gallbladder,Cancers, Gall Bladder,Cancers, Gallbladder,Gall Bladder Cancers,Gallbladder Cancers,Gallbladder Neoplasm,Neoplasm, Gallbladder
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016159	Tumor Suppressor Protein p53	Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.	p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53