ABSTRACT Recently, it was shown that the oncogenic activation of _BRAF_, a member of the RAS/RAF family of kinases, by the V600E mutation is characteristic for sporadic colon tumors with

microsatellite instability. Further, it was shown to associate with the silencing of the mismatch repair (MMR) gene _MLH1_ by hypermethylation. Moreover, _BRAF_ mutations proved to be absent

in tumors from hereditary nonpolyposis colorectal cancer syndrome (HNPCC) families with germline mutations in the MMR genes _MLH1_ and _MSH2_. These data suggest that the oncogenic

activation of _BRAF_ is involved only in sporadic colorectal tumorigenesis. In order to further support this hypothesis, we have extended the analysis of the _BRAF_ gene to a different

mutations were detected in 14 tumors from HNPCC patients with germline mutations in _MSH6_. Further, no mutations of _BRAF_ were found in tumors from 23 MMR-negative families, from which 13

fulfilled the Amsterdam criteria (HNPCC) and 10 were suspected for HNPCC as they were positive for the Bethesda criteria. Overall, our data reinforce the concept that _BRAF_ is not involved

in the colorectal tumorigenesis of HNPCC. The detection of a positive _BRAF-V600E_ mutation in a colorectal cancer suggests a sporadic origin of the disease and the absence of germline

alterations of _MLH1_, _MSH2_ and also of _MSH6._ These findings have a potential impact in the genetic testing for HNPCC diagnostics and suggest a potential use of BRAF as exclusion

criteria for HNPCC or as a molecular marker of sporadic cancer. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS _MUTYH_-ASSOCIATED TUMOR SYNDROME: THE OTHER FACE OF MAP Article 14 April 2022

EXOME SEQUENCING REVEALED COMPARABLE FREQUENCIES OF _RNF43_ AND _BRAF_ MUTATIONS IN MIDDLE EASTERN COLORECTAL CANCER Article Open access 30 July 2022 GERMLINE NPAT INACTIVATING VARIANTS AS

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ACKNOWLEDGEMENTS This work was supported by Grants from the Dutch Cancer Society (RUG 1997-1544 and RUG 2002-2678); the Spanish Fondo de Investigaciones Sanitarias (FlS 01/1350), Spain; the

Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of

Health, Labor, and Welfare of Japan; and the Fundação para a Ciēncia e Tecnologia (POCTI/SAU-OBS/56921/2004), Portugal. ED was supported by a fellowship from the Spanish Fondo de

Investigaciones Sanitarias. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Molecular Oncology and Aging Research, Centre d'Investigacions en Bioquímica i Biologia Molecular (CIBBIM),

Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona, 08035, Spain Enric Domingo, Eloi Espín, Manel Armengol & Simó Schwartz Jr * Department of Medical

Genetics, University of Groningen, A Deusinglaan 4, 9713 AW, Groningen, The Netherlands Renée C Niessen & Robert M W Hofstra * Instituto de Patologia e Imunologia Molecular da

Universidade do Porto (IPATIMUP), 4200-465, Porto, Portugal Carla Oliveira, Catia Moutinho & Raquel Seruca * Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki,

00014, Helsinki, Finland Pia Alhopuro & Lauri A Aaltonen * Department of Clinical Genetics, University Hospital Groningen, Groningen, The Netherlands Rolf H Sijmons * Department of

Gastroenterology, University Hospital Groningen, Groningen, The Netherlands Jan H Kleibeuker * First Department of Internal Medicine, Sapporo Medical University, S.1, W.16, Chuo-ku, Sapporo,

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Domingo, E., Niessen, R., Oliveira, C. _et al._ _BRAF-V600E_ is not involved in the colorectal tumorigenesis of HNPCC in patients with

functional _MLH1_ and _MSH2_ genes. _Oncogene_ 24, 3995–3998 (2005). https://doi.org/10.1038/sj.onc.1208569 Download citation * Received: 19 October 2004 * Revised: 25 January 2005 *

Accepted: 28 January 2005 * Published: 21 March 2005 * Issue Date: 02 June 2005 * DOI: https://doi.org/10.1038/sj.onc.1208569 SHARE THIS ARTICLE Anyone you share the following link with will

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content-sharing initiative KEYWORDS * HNPCC * _BRAF_ * _MSH6_