Braf-v600e is not involved in the colorectal tumorigenesis of hnpcc in patients with functional mlh1 and msh2 genes

Braf-v600e is not involved in the colorectal tumorigenesis of hnpcc in patients with functional mlh1 and msh2 genes

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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 subset of HNPCC families without germline mutations in _MLH1_ and _MSH2_. _BRAF-V600E_ mutations were analysed by automatic sequencing in 38 tumors from HNPCC families with germline mutations in the _MSH6_ gene and also in HNPCC (suspected) families that do not have mutations in the MMR genes _MLH1, MSH2_ and _MSH6_. All patients belong to different families. No 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 OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about 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 CAUSE OF HEREDITARY COLORECTAL CANCER Article 22 May 2024 REFERENCES * Berends MJ, Wu Y, Sijmons RH, Mensink RG, van der Sluis T, Hordijk-Hos JM, de Vries EG, Hollema H, Karrenbeld A, Buys CH, van der Zee AG, Hofstra RM and Kleibeuker JH . (2002). _Am. J. Hum. Genet._, 70, 26–37. * Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodriguez-Bigas MA, Fodde R, Ranzani GN and Srivastava SA . (1998). _Cancer Res._, 58, 5248–5257. * Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JWC, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR and Futreal PA . (2002). _Nature_, 417, 949–954. * Deng G, Bell I, Crawley S, Gum J, Terdiman JP, Allen BA, Truta B, Sleisenger MH and Kim YS . (2004). _Clin. Cancer Res._, 10, 191–195. * Di Fiore F, Charbonnier F, Martin C, Frerot S, Olschwang S, Wang Q, Boisson C, Buisine MP, Nilbert M, Lindblom A and Frebourg T . (2004). _J. Med. Genet._, 41, 18–20. * Domingo E, Espín E, Armengol M, Oliveira C, Pinto M, Duval A, Brennetot C, Seruca R, Hamelin R, Yamamoto H and Schwartz Jr S . (2004a). _Genes Chrom. Cancer_, 39, 138,142. * Domingo E, Laiho P, Ollikainen M, Pinto M, Wang L, French AJ, Westra J, Frebourg T, Espín E, Armengol M, Hamelin R, Yamamoto H, Hofstra RMW, Seruca R, Lindblom A, Peltomäki P, Thibodeau SN, Aaltonen LA and Schwartz Jr S . (2004b). _J. Med. Genet._, 41, 664–668. * Gille JJ, Hogervorst FB, Pals G, Wijnen JT, van Schooten RJ, Dommering CJ, Meijer GA, Craanen ME, Nederlof PM, de Jong D, McElgunn CJ, Schouten JP and Menko FH . (2002). _Br. J. Cancer_, 87, 892–897. * Marra G and Boland CR . (1995). _J. Natl. Cancer Inst._, 87, 1114–1125. * Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, Igari T, Koike M, Chiba M and Mori T . (1997). _Nat. Genet._, 17, 271–272. * Oliveira C, Pinto M, Duval A, Brennetot C, Domingo E, Espín E, Armengol M, Yamamoto H, Hamelin R, Seruca R and Schwartz Jr S . (2003). _Oncogene_, 22, 9192–9196. * Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE . (2002). _Nature_, 418, 934. * Rodriguez-Bigas MA, Boland CR, Hamilton SR, Henson DE, Jass JR, Khan PM, Lynch H, Perucho M, Smyrk T, Sobin L and Srivastava SA . (1997). _J. Natl. Cancer Inst._, 89, 1758–1762. * Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN and Srivastava S . (2004). _J. Natl. Cancer Inst._, 96, 261–268. * Vasen HFA, Mecklin J-P, Khan PM and Lynch HT . (1991). _Dis. Colon Rectum_, 34, 424–425. * Vasen HFA, Watson P, Mecklin J-P and Lynch HT . (1999). _Gastroenterology_, 116, 1453–1456. * Wahlberg S, Liu T, Lindblom P and Lindblom A . (1999). _Genet. Test._, 3, 259–264. * Wang L, Cunningham JM, Winters JL, Guenther JC, French AJ, Boardman LA, Burgart LJ, McDonnell SK, Schaid DJ and Thibodeau SN . (2003). _Cancer Res._, 63, 5209–5212. * Wijnen J, de Leeuw W, Vasen H, van der Klift H, Moller P, Stormorken A, Meijers-Heijboer H, Lindhout D, Menko F, Vossen S, Moslein G, Tops C, Brocker-Vriends A, Wu Y, Hofstra R, Sijmons R, Cornelisse C, Morreau H and Fodde R . (1999). _Nat Genet._, 23, 142–144. Download references 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, 060-8543, Japan Kohzoh Imai & Hiroyuki Yamamoto Authors * Enric Domingo View author publications You can also search for this author inPubMed Google Scholar * Renée C Niessen View author publications You can also search for this author inPubMed Google Scholar * Carla Oliveira View author publications You can also search for this author inPubMed Google Scholar * Pia Alhopuro View author publications You can also search for this author inPubMed Google Scholar * Catia Moutinho View author publications You can also search for this author inPubMed Google Scholar * Eloi Espín View author publications You can also search for this author inPubMed Google Scholar * Manel Armengol View author publications You can also search for this author inPubMed Google Scholar * Rolf H Sijmons View author publications You can also search for this author inPubMed Google Scholar * Jan H Kleibeuker View author publications You can also search for this author inPubMed Google Scholar * Raquel Seruca View author publications You can also search for this author inPubMed Google Scholar * Lauri A Aaltonen View author publications You can also search for this author inPubMed Google Scholar * Kohzoh Imai View author publications You can also search for this author inPubMed Google Scholar * Hiroyuki Yamamoto View author publications You can also search for this author inPubMed Google Scholar * Simó Schwartz Jr View author publications You can also search for this author inPubMed Google Scholar * Robert M W Hofstra View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Simó Schwartz Jr. RIGHTS AND PERMISSIONS Reprints and 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 be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * HNPCC * _BRAF_ * _MSH6_

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


subset of HNPCC families without germline mutations in _MLH1_ and _MSH2_. _BRAF-V600E_ mutations were analysed by automatic sequencing in 38 tumors from HNPCC families with germline


mutations in the _MSH6_ gene and also in HNPCC (suspected) families that do not have mutations in the MMR genes _MLH1, MSH2_ and _MSH6_. All patients belong to different families. No


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


OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this article * Purchase on


SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about


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


CAUSE OF HEREDITARY COLORECTAL CANCER Article 22 May 2024 REFERENCES * Berends MJ, Wu Y, Sijmons RH, Mensink RG, van der Sluis T, Hordijk-Hos JM, de Vries EG, Hollema H, Karrenbeld A, Buys


CH, van der Zee AG, Hofstra RM and Kleibeuker JH . (2002). _Am. J. Hum. Genet._, 70, 26–37. * Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ,


Rodriguez-Bigas MA, Fodde R, Ranzani GN and Srivastava SA . (1998). _Cancer Res._, 58, 5248–5257. * Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett


MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H,


Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JWC, Leung SY, Yuen


ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR and Futreal PA . (2002). _Nature_, 417, 949–954. * Deng G, Bell I, Crawley S, Gum J, Terdiman


JP, Allen BA, Truta B, Sleisenger MH and Kim YS . (2004). _Clin. Cancer Res._, 10, 191–195. * Di Fiore F, Charbonnier F, Martin C, Frerot S, Olschwang S, Wang Q, Boisson C, Buisine MP,


Nilbert M, Lindblom A and Frebourg T . (2004). _J. Med. Genet._, 41, 18–20. * Domingo E, Espín E, Armengol M, Oliveira C, Pinto M, Duval A, Brennetot C, Seruca R, Hamelin R, Yamamoto H and


Schwartz Jr S . (2004a). _Genes Chrom. Cancer_, 39, 138,142. * Domingo E, Laiho P, Ollikainen M, Pinto M, Wang L, French AJ, Westra J, Frebourg T, Espín E, Armengol M, Hamelin R, Yamamoto H,


Hofstra RMW, Seruca R, Lindblom A, Peltomäki P, Thibodeau SN, Aaltonen LA and Schwartz Jr S . (2004b). _J. Med. Genet._, 41, 664–668. * Gille JJ, Hogervorst FB, Pals G, Wijnen JT, van


Schooten RJ, Dommering CJ, Meijer GA, Craanen ME, Nederlof PM, de Jong D, McElgunn CJ, Schouten JP and Menko FH . (2002). _Br. J. Cancer_, 87, 892–897. * Marra G and Boland CR . (1995). _J.


Natl. Cancer Inst._, 87, 1114–1125. * Miyaki M, Konishi M, Tanaka K, Kikuchi-Yanoshita R, Muraoka M, Yasuno M, Igari T, Koike M, Chiba M and Mori T . (1997). _Nat. Genet._, 17, 271–272. *


Oliveira C, Pinto M, Duval A, Brennetot C, Domingo E, Espín E, Armengol M, Yamamoto H, Hamelin R, Seruca R and Schwartz Jr S . (2003). _Oncogene_, 22, 9192–9196. * Rajagopalan H, Bardelli A,


Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE . (2002). _Nature_, 418, 934. * Rodriguez-Bigas MA, Boland CR, Hamilton SR, Henson DE, Jass JR, Khan PM, Lynch H, Perucho M, Smyrk T,


Sobin L and Srivastava SA . (1997). _J. Natl. Cancer Inst._, 89, 1758–1762. * Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin


R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN and Srivastava S . (2004). _J. Natl. Cancer


Inst._, 96, 261–268. * Vasen HFA, Mecklin J-P, Khan PM and Lynch HT . (1991). _Dis. Colon Rectum_, 34, 424–425. * Vasen HFA, Watson P, Mecklin J-P and Lynch HT . (1999). _Gastroenterology_,


116, 1453–1456. * Wahlberg S, Liu T, Lindblom P and Lindblom A . (1999). _Genet. Test._, 3, 259–264. * Wang L, Cunningham JM, Winters JL, Guenther JC, French AJ, Boardman LA, Burgart LJ,


McDonnell SK, Schaid DJ and Thibodeau SN . (2003). _Cancer Res._, 63, 5209–5212. * Wijnen J, de Leeuw W, Vasen H, van der Klift H, Moller P, Stormorken A, Meijers-Heijboer H, Lindhout D,


Menko F, Vossen S, Moslein G, Tops C, Brocker-Vriends A, Wu Y, Hofstra R, Sijmons R, Cornelisse C, Morreau H and Fodde R . (1999). _Nat Genet._, 23, 142–144. Download references


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,


060-8543, Japan Kohzoh Imai & Hiroyuki Yamamoto Authors * Enric Domingo View author publications You can also search for this author inPubMed Google Scholar * Renée C Niessen View


author publications You can also search for this author inPubMed Google Scholar * Carla Oliveira View author publications You can also search for this author inPubMed Google Scholar * Pia


Alhopuro View author publications You can also search for this author inPubMed Google Scholar * Catia Moutinho View author publications You can also search for this author inPubMed Google


Scholar * Eloi Espín View author publications You can also search for this author inPubMed Google Scholar * Manel Armengol View author publications You can also search for this author


inPubMed Google Scholar * Rolf H Sijmons View author publications You can also search for this author inPubMed Google Scholar * Jan H Kleibeuker View author publications You can also search


for this author inPubMed Google Scholar * Raquel Seruca View author publications You can also search for this author inPubMed Google Scholar * Lauri A Aaltonen View author publications You


can also search for this author inPubMed Google Scholar * Kohzoh Imai View author publications You can also search for this author inPubMed Google Scholar * Hiroyuki Yamamoto View author


publications You can also search for this author inPubMed Google Scholar * Simó Schwartz Jr View author publications You can also search for this author inPubMed Google Scholar * Robert M W


Hofstra View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Simó Schwartz Jr. RIGHTS AND PERMISSIONS Reprints and


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


be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt


content-sharing initiative KEYWORDS * HNPCC * _BRAF_ * _MSH6_