caa a22 4500 445331100 CHVBK 20180317142737.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10689-011-9473-7 doi (NATIONALLICENCE)springer-10.1007/s10689-011-9473-7 Familial colorectal cancer type X syndrome: two distinct molecular entities? [Elektronische Daten] [Inês Francisco, Cristina Albuquerque, Pedro Lage, Hélio Belo, Inês Vitoriano, Bruno Filipe, Isabel Claro, Sara Ferreira, Paula Rodrigues, Paula Chaves, Carlos Leitão, António Pereira] In a fraction of families fulfilling the Amsterdam criteria for hereditary non-polyposis colorectal cancer, colorectal cancers are microsatellite stable and DNA mismatch repair gene (MMR) mutations are not found. These families were designated as familial colorectal cancer type X (FCCTX). We aimed to characterise a group of FCCTX families defined by the Amsterdam criteria and MSS tumours at clinical and molecular level. Twenty-four tumours from 15 FCCTX families were analysed for loss of known tumour suppressor gene (TSG) loci (APC, TP53, SMAD4 and DCC), MGMT and MMR genes promoter methylation, and also APC and KRAS somatic mutations. FCCTX families presented specific clinical features: absence of endometrial tumours, high adenoma/carcinoma ratio (1.91) and prevalence of rectal cancers (13/27, 48%). New molecular features were found: the majority of FCCTX tumours (13/18; 72%) presented TSG loss. TSG loss positive tumours presented frequent APC and KRAS somatic mutations and MGMT methylation [10/13 (77%), 7/13 (54%) and 6/11 (54%), respectively]. In TSG loss negative tumours (5/18; 28%), the same molecular events were found in 2/5 (40%), 2/5 (40%) and 1/3 (33%) tumours, respectively. Transition mutations in KRAS were more frequent among MGMT methylated tumours than in unmethylated [5/8 (63%) vs. 1/10 (10%), P=0.03]. Although sharing similar clinical features, at least two different molecular entities should exist among FCCTX families, one whose tumours present frequent TSG loss, APC and KRAS somatic mutations, and MGMT promoter methylation, and a second, lesser predominant, with no evidence of TSG loss and rarely presenting promoter methylation. Springer Science+Business Media B.V., 2011 Colorectal cancer nationallicence Familial colorectal cancer type X nationallicence Lynch syndrome nationallicence Francisco Inês Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut Albuquerque Cristina Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut Lage Pedro Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut Belo Hélio Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut Vitoriano Inês Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut Filipe Bruno Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut Claro Isabel Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut Ferreira Sara Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut Rodrigues Paula Clínica de Risco Familiar, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut Chaves Paula Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut Leitão Carlos Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut Pereira António Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut Familial Cancer Springer Netherlands 10/4(2011-12-01), 623-631 1389-9600 10:4<623 2011 10 10689 https://doi.org/10.1007/s10689-011-9473-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-011-9473-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Francisco Inês Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut NATIONALLICENCE 700 1- Albuquerque Cristina Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut NATIONALLICENCE 700 1- Lage Pedro Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut NATIONALLICENCE 700 1- Belo Hélio Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut NATIONALLICENCE 700 1- Vitoriano Inês Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut NATIONALLICENCE 700 1- Filipe Bruno Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Rua Professor Lima Basto, 1099-023, Lisbon, Portugal aut NATIONALLICENCE 700 1- Claro Isabel Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut NATIONALLICENCE 700 1- Ferreira Sara Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut NATIONALLICENCE 700 1- Rodrigues Paula Clínica de Risco Familiar, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut NATIONALLICENCE 700 1- Chaves Paula Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut NATIONALLICENCE 700 1- Leitão Carlos Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut NATIONALLICENCE 700 1- Pereira António Serviço de Gastrenterologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE (IPOLFG, EPE), Lisbon, Portugal aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/4(2011-12-01), 623-631 1389-9600 10:4<623 2011 10 10689 Metadata rights reserved Springer special 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