RESUMEN
Familial adenomatous polyposis (FAP) is a hereditary syndrome characterized by the presence of multiple adenomatous polyps in the colon. The main cause of the disease is a germline mutation in the APC gene. Here we report 4 unrelated FAP patients with different large deletions in the APC gene detected by Multiplex Ligation-dependent Probe Amplification (MLPA) method: deletion of exons 7-15, deletion of promoters B, A, and 5'-UTR region and deletion of promoter B (in 2 patients). The deletion of promoters B, A, and 5'-UTR was not described in the literature earlier, so we report it for the first time. In 2 families with promoter B deletion, we could identify the tendency for decreasing the age of disease manifestation in each next generation, in contrast to the previous one. The incidence of large deletions in APC among Russian patients with FAP reached 4.8% and our finding suggests the need to study this gene by MLPA in "no mutation patients" after Sanger's sequencing.
Asunto(s)
Poliposis Adenomatosa del Colon , Genes APC , Eliminación de Secuencia , Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon/genética , Mutación de Línea Germinal , Humanos , Regiones Promotoras Genéticas , Federación de RusiaRESUMEN
MutYH-associated polyposis is the only polyposis syndrome with an autosomal recessive type of inheritance, often phenotypically similar to a weakened form of familial adenomatous polyposis. For the development of the disease mutations in both alleles of the gene are required, but an increased risk of developing colorectal cancer in carriers of monoallelic mutations is noted. The diagnosis of MutYH-associated polyposis should be suspected in a patient with colorectal cancer over 45 years old on the background of polyps in the colon. The review presents modern algorithms for diagnostic and treatment of the disease.
Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/genética , Neoplasias Colorrectales/genética , ADN Glicosilasas/genética , Predisposición Genética a la Enfermedad/genética , Anciano , Anciano de 80 o más Años , Alelos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , FenotipoRESUMEN
Turcot syndrome is a rare hereditary syndrome characterized by a combination of brain tumors and colorectal cancer. According to the literature, about 150 such cases have been reported. This article presents a rare clinical case and a literature review.
Asunto(s)
Neoplasias Encefálicas , Neoplasias Colorrectales , Síndrome de Gardner , Neoplasias Encefálicas/diagnóstico , Neoplasias Colorrectales/diagnóstico , Femenino , Síndrome de Gardner/diagnóstico , Humanos , Síndromes Neoplásicos Hereditarios/diagnósticoRESUMEN
Peutz-Jeghers syndrome is a rare hereditary syndrome characterized by presence of hamartoma polyps in intestinal tract and usually by mucocutaneous pigmentation. Clinical-genetic characteristics of Russian patients with Peutz-Jeghers syndrome were studied for the first time. Four germline mutations in STK11gene were found in probands from six families and three of them had not been described previously. Clinical pattern of disease in Russian patients included: frequent polyposis of colon and stomach (62,5% and 75%, respectively) along with small bowel; frequent presence of malignant tumors (62,5%). These clinical aspects can help physicians to find out Peutz-Jeghers syndrome. Molecular-genetic testing of individuals should be recommended.
Asunto(s)
Mutación de Línea Germinal , Proteínas de Neoplasias/genética , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinasas/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Síndrome de Peutz-Jeghers/enzimología , Síndrome de Peutz-Jeghers/patología , Proyectos Piloto , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
The expression levels of microRNAs miR-200c and miR-145 in two groups of colorectal cancer differing by the presence/absence of epithelial-mesenchymal transition (EMF) were studied. In the EMF-positive cancer, the level of miR-145 is increased, whereas the level of miR-200c is reduced. The reverse situation is observed in the EMI-negative cancer. MiR-145 can serve as a marker of the mesenchymal subtype of cancer. Gene expression profiles and microRNAs allow prognostically unfavorable tumors of the mesenchymal subtype to be distinguished.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Transición Epitelial-Mesenquimal , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Colorectal cancer is highly metastatic even when the tumors are small. To disseminate, cells use a complex and multistage process known as the epithelial-mesenchymal transition, in which epithelial phenotype is transformed into mesenchymal phenotype. The objective of this study is to describe the epithelial-mesenchymal transition in terms of gene expression profile and somatic alterations in samples of colorectal cancer with or without peritoneal carcinomatosis. We analyzed samples taken from 38 patients with colorectal cancer (stages II-IV) and samples from 20 patients with colorectal cancer complicated by peritoneal carcinomatosis. The expression of ZEB1, ZEB2, CDH1, VIM, and SNAI1 was analyzed by real-time PCR. KRAS/BRAF mutations were mapped using sequencing. Microsatellite instability was evaluated by fragment analysis. Epithelial-mesenchymal transition was detected in 6 out of 38 samples of colorectal cancer (stages II-IV), 7 out of 20 tumors from patients with peritoneal carcinomatosis, and 19 out of 20 samples taken from carcinomatous nodules. Tumors of the mesenchymal subtype displayed high frequency of somatic mutations, microsatellite stability, and low degree of differentiation. The identification of epithelial-mesenchymal transition may be used as a marker of high metastatic potential, which is particularly relevant at early stages of tumor growth.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Mutación/genética , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/complicaciones , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Inestabilidad de Microsatélites , Persona de Mediana Edad , Tasa de Mutación , Estadificación de Neoplasias , Neoplasias Peritoneales/complicaciones , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Proteínas ras/genéticaRESUMEN
Clinical and genetic analysis of 24 Russian patients with attenuated form of family colon adenomatosis was undertaken. On the basis of obtained clinical and genetic data it was defined the algorithm of therapeutic measures in this group of patients--from dynamic monitoring or endoscopic polypectomy to performing extensive resections of the colon in situations associated with cancer development, an increase of the intensity of growth of polyps or an appearance of villous lesions. Some of the patients had molecular-genetics causes of a weakened form of family adenomatosis.