RESUMO
INTRODUCTION: Hereditary Non-Polyposis Colorectal Cancer is an inherited disease with deleterious germline mutations in the DNA mismatch repair genes causing the development of colon cancer and other malignancies. This is the first study in Hungary screening the population of our colorectal cancer patients in order to identify the prevalence of the disease. METHODS: In families who met the Modified Amsterdam and Bethesda Criteria the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis. Those cases which showed high microsatellite instability underwent DNA sequencing and multiple ligation dependent probe amplification. RESULTS: Of the 1576 patients with colorectal cancer underwent screening for the modified Amsterdam and Bethesda criteria, 69 (4.4%) and 166 (10.5%) fulfilled the criteria respectively. 15 patients (31%) of the Amsterdam positive group and 19 patients from the Bethesda positive (18.1%) were MSI-H. There were 8 pathogenic mutations identified in 9 families (60%) in the Amsterdam positive group. 5 mutations were found in 5 families (26%) in the Bethesda positive group. 12 pathogenic mutations were identified, two of these are newly identified, and being published first in this work. These two new mutations were located on MLH1 (g.31276_35231del) and MSH2 (c.969_970delTC) genes. CONCLUSION: The prevalence of the mutations in the MLH1 and MSH2 genes was almost equal in our Hungarian colorectal cancer patients. One mutation in the MLH1 gene (c.143A > C; p.Q48P) was identified in three different families. Whether this mutation is the most frequent in the Hungarian population is still unidentified and warrant further investigation.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Mutação em Linhagem Germinativa/genética , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Adulto , Idoso , Estudos de Coortes , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Hungria , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Estudos Retrospectivos , Análise de Sequência de DNA , População BrancaRESUMO
Hereditary Nonpolyposis Colorectal Carcinoma (HNPCC) is the most frequent inherited disease which can lead to the development of tumors in the colon and other locations. Its genetic basis is related to the germline mutation of the Mismatch Repair (MMR) genes. Muir-Torre syndrome is considered one of the subtypes of this disease, in which the HNPCC tumor spectrum is frequently associated with sebaceous carcinoma of the skin or keratoacanthoma. A 57 years old male patient is presented with a mucinous carcinoma of the caecum and an adenocarcinoma of the pancreas head. A malignant sebaceous carcinoma was removed from his left neck area. His family history was significant for two cases of colon carcinoma, two cases of stomach cancer and a case of metacron endometrial and skin tumor as well. Both the colon carcinoma and the skin tumor proved to be microsatellite unstable. An Arg>Pro switch missense mutation was found in codon 265 of the hMLH1 gene. This error was found in 4 other members of his family. The detected genetic alteration was considered pathogenic and was not published yet in English literature. The significance of this particular case is the rare tumor association in a patient with Muir-Torre syndrome (MTS). In cases of sebaceous skin lesions, evaluation of family history is of utmost importance in the early detection of HNPCC and in the follow up care of family members with the particular mutation.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Síndrome de Muir-Torre/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Neoplasias do Ceco/genética , Neoplasias do Ceco/patologia , Saúde da Família , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Muir-Torre/patologia , Proteína 1 Homóloga a MutL , Proteínas MutL , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , LinhagemRESUMO
A rare case is reported with a large foreign body in the upper gastrointestinal tract. The 32-year-old man accidentally swallowed his toothbrush which was successfully removed via endoscopy using polypectomy snare under local anesthesia.
