RESUMO
Gastric cancer is the second most common cause of cancer death worldwide. Environmental as well as genetic factors have been shown to be involved in its genesis. Among genetic factors, loss of function of a tumor suppressive gene named promyelocytic leukemia (PML) has been demonstrated in gastric cancer. In order to cast light in the mechanism by which PML protein is under-expressed in gastric cancer cells, we analyzed all exons and intron-exon boundaries of PML gene in 50 formalin-fixed paraffin-embedded tissue blocks from gastric carcinoma tumors by means of PCR-SSCP and CSGE, with direct sequencing of abnormally shifted bands. We found a novel sequence variant of unknown significance localized in intron 5 in 3 samples (c.1398+84delA). We did not detect any deleterious mutations of the PML gene. This study shows that PML mutations may not contribute to gastric adenocarcinoma development. Post-translational modifications or protein degradation might be mechanisms by which PML is not expressed in gastric tumors.
Assuntos
Adenocarcinoma/genética , Mutação , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletroforese , Éxons , Feminino , Predisposição Genética para Doença , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteína da Leucemia Promielocítica , Processamento de Proteína Pós-Traducional , Proteólise , Análise de Sequência de DNARESUMO
Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, impaired utilization of glucose and galactose, rickets, and severe short stature. It has been shown to be caused by mutations in GLUT2 gene, a member of the facilitative glucose transporter family. Here, we report an Iranian family with 2 affected siblings. The clinical findings in the patients include developmental delay, failure to thrive, hepatomegaly, enlarged kidneys and rickets. A novel 6 nucleotide deletion (c.1061_1066del6, p.V355_S356del2) is shown to be segregated with the disease in this family.
Assuntos
Síndrome de Fanconi/genética , Transportador de Glucose Tipo 2/genética , Sequência de Bases , Criança , Feminino , Homozigoto , Humanos , Lactente , Irã (Geográfico) , Masculino , Análise de Sequência de DNA , Deleção de SequênciaRESUMO
Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare autosomal recessive metabolic disorder caused by mutations in the GALNT3 and FGF23 genes. The main features of this disorder include painful swelling of long bones, increased renal reabsorption of phosphate but normal renal function and vitamin D and parathormone levels. Previously, we reported a novel missense mutation in the FGF23 gene in a patient suffering from HHS. In the present report, we demonstrated the same mutation (c.471C>A) in two other cases of HHS with similar clinical manifestations. As this nucleotide change has not been reported previously, it can be a population specific mutation in Iran that can facilitate carrier testing and prenatal diagnosis of HHS.
Assuntos
Fatores de Crescimento de Fibroblastos/genética , Hiperostose/genética , Hiperfosfatemia/genética , Mutação de Sentido Incorreto , Adolescente , Criança , Consanguinidade , Feminino , Fator de Crescimento de Fibroblastos 23 , Frequência do Gene , Predisposição Genética para Doença , Humanos , Hiperostose/epidemiologia , Hiperfosfatemia/epidemiologia , Irã (Geográfico)/epidemiologia , LinhagemRESUMO
Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare autosomal recessive metabolic disorder, characterized by recurrent painful swelling of long bones, periosteal new bone formation and cortical hyperostosis or intramedullary sclerosis, hyperphosphatemia and low intact fibroblast growth factor 23 (FGF23) protein levels. It is caused by mutations in 2 genes, N-acetylgalactosaminyltransferase 3 (GalNAc-transferase; GALNT3) and FGF23. We have performed mutation analysis of the GALNT3 and FGF23 genes in a patient with HHS and detected a homozygous mutation in exon 3 of FGF23 gene (NM_020638.2: c.471C>A) which results in amino acid change from phenylalanine 157 to leucin (p.F157L) in receptor interaction site.
Assuntos
Fatores de Crescimento de Fibroblastos/genética , Hiperostose/genética , Hiperfosfatemia/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Pré-Escolar , Simulação por Computador , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/química , Homozigoto , Humanos , Masculino , N-Acetilgalactosaminiltransferases/genética , Conformação Proteica , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
Cancer-testis (CT) antigens are tumor-associated antigens attracting immunologists for their possible application in the immunotherapy of cancer. Several clinical trials have assessed their therapeutic potentials in cancer patients. Breast cancers, especially triple-negative cancers are among those with significant expression of CT genes. Identification of CT genes with high expression in cancer patients is the prerequisite for any immunotherapeutic approach. CT genes have gained attention not only for immunotherapy of cancer patients, but also for immunoprevention in high-risk individuals. Many CT genes have proved to be immunogenic in breast cancer patients suggesting the basis for the development of polyvalent vaccines.