Age-dependent performance of BRAF mutation testing in Lynch syndrome diagnostics.


Journal

International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124

Informations de publication

Date de publication:
15 11 2020
Historique:
received: 08 05 2020
revised: 17 07 2020
accepted: 03 08 2020
pubmed: 3 9 2020
medline: 17 4 2021
entrez: 3 9 2020
Statut: ppublish

Résumé

BRAF V600E mutations have been reported as a marker of sporadic microsatellite instability (MSI) colorectal cancer (CRC). Current international diagnostic guidelines recommend BRAF mutation testing in MSI CRC patients to predict low risk of Lynch syndrome (LS). We evaluated the age-specific performance of BRAF testing in LS diagnostics. We systematically compared the prevalence of BRAF mutations in LS-associated CRCs and unselected MSI CRCs in different age groups as available from published studies, databases and population-based patient cohorts. Sensitivity/specificity analysis of BRAF testing for exclusion of LS and cost calculations were performed. Among 969 MSI CRCs from LS carriers in the literature and German HNPCC Consortium, 15 (1.6%) harbored BRAF mutations. Six of seven LS patients with BRAF-mutant CRC and reported age were <50 years. Among 339 of 756 (44.8%) of BRAF mutations detected in unselected MSI CRC, only 2 of 339 (0.6%) BRAF mutations were detected in patients <50 years. The inclusion of BRAF testing led to high risk of missing LS patients and increased costs at age <50 years. BRAF testing in patients <50 years carries a high risk of missing a hereditary cancer predisposition and is cost-inefficient. We suggest direct referral of MSI CRC patients <50 years to genetic counseling without BRAF testing.

Identifiants

pubmed: 32875553
doi: 10.1002/ijc.33273
doi:

Substances chimiques

Genetic Markers 0
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2801-2810

Informations de copyright

© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.

Références

Salovaara R, Loukola A, Kristo P, et al. Population-based molecular detection of hereditary nonpolyposis colorectal cancer. J Clin Oncol. 2000;18:2193-2200.
Moreira L, Balaguer F, Lindor N, et al. Identification of Lynch syndrome among patients with colorectal cancer. Jama. 2012;308:1555-1565.
de la Chapelle A. Microsatellite instability. N Engl J Med. 2003;349:209-210.
Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004;96:261-268.
Phipps AI, Limburg PJ, Baron JA, et al. Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology. 2015;148:77-87.e2.
Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology. 2010;138:2088-2100.
Vasen HF, Moslein G, Alonso A, et al. Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer). J Med Genet. 2007;44:353-362.
Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248-5257.
Vasen HF, Blanco I, Aktan-Collan K, et al. Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts. Gut. 2013;62:812-823.
Domingo E, Laiho P, Ollikainen M, et al. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. J Med Genet. 2004;41:664-668.
Giardiello FM, Allen JI, Axilbund JE, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer. Am J Gastroenterol. 2014;109:1159-1179.
Deng G, Bell I, Crawley S, et al. BRAF mutation is frequently present in sporadic colorectal cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer. Clin Cancer Res. 2004;10:191-195.
Loughrey MB, Waring PM, Tan A, et al. Incorporation of somatic BRAF mutation testing into an algorithm for the investigation of hereditary non-polyposis colorectal cancer. Fam Cancer. 2007;6:301-310.
Miyaki M, Iijima T, Yamaguchi T, Kadofuku T, Funata N, Mori T. Both BRAF and KRAS mutations are rare in colorectal carcinomas from patients with hereditary nonpolyposis colorectal cancer. Cancer Lett. 2004;211:105-109.
Newton K, Jorgensen NM, Wallace AJ, et al. Tumour MLH1 promoter region methylation testing is an effective prescreen for Lynch syndrome (HNPCC). J Med Genet. 2014;51:789-796.
Walsh MD, Buchanan DD, Walters R, et al. Analysis of families with Lynch syndrome complicated by advanced serrated neoplasia: the importance of pathology review and pedigree analysis. Fam Cancer. 2009;8:313-323.
Lagerstedt Robinson K, Liu T, Vandrovcova J, et al. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 2007;99:291-299.
Parsons MT, Buchanan DD, Thompson B, Young JP, Spurdle AB. Correlation of tumour BRAF mutations and MLH1 methylation with germline mismatch repair (MMR) gene mutation status: a literature review assessing utility of tumour features for MMR variant classification. J Med Genet. 2012;49:151-157.
Thompson BA, Goldgar DE, Paterson C, et al. A multifactorial likelihood model for MMR gene variant classification incorporating probabilities based on sequence bioinformatics and tumor characteristics: a report from the colon cancer family registry. Hum Mutat. 2013;34:200-209.
Brenner H, Jansen L, Ulrich A, Chang-Claude J, Hoffmeister M. Survival of patients with symptom- and screening-detected colorectal cancer. Oncotarget. 2016;7:44695-44704.
Hoffmeister M, Jansen L, Rudolph A, et al. Statin use and survival after colorectal cancer: the importance of comprehensive confounder adjustment. J Natl Cancer Inst. 2015;107:djv045.
Brenner H, Chang-Claude J, Jansen L, et al. Reduced risk of colorectal cancer up to 10 years after screening, surveillance, or diagnostic colonoscopy. Gastroenterology. 2014;146:709-717.
Cerami E, Gao J, Dogrusoz U, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401-404.
Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):pl1.
Blaker H, Alwers E, Arnold A, et al. The association between mutations in BRAF and colorectal cancer-specific survival depends on microsatellite status and tumor stage. Clin Gastroenterol Hepatol. 2019;17:455-462.
Morak M, Ibisler A, Keller G, et al. Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation. J Med Genet. 2018;55:240-248.
Snowsill T, Huxley N, Hoyle M, et al. A systematic review and economic evaluation of diagnostic strategies for Lynch syndrome. Health Technol Assess. 2014;18:1-406.
Ladabaum U, Wang G, Terdiman J, et al. Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med. 2011;155:69-79.
Di Marco M, D'Andrea E, Panic N, et al. Which Lynch syndrome screening programs could be implemented in the "real world"? A systematic review of economic evaluations. Genet Med. 2018;20:1131-1144.
Cenin DR, Naber SK, Lansdorp-Vogelaar I, et al. Costs and outcomes of Lynch syndrome screening in the Australian colorectal cancer population. J Gastroenterol Hepatol. 2018;33:1737-1744.
Snowsill T, Huxley N, Hoyle M, et al. A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients. BMC Cancer. 2015;15:313.
Porkka N, Lahtinen L, Ahtiainen M, et al. Epidemiological, clinical and molecular characterization of Lynch-like syndrome: a population-based study. Int J Cancer. 2019;145:87-98.
Gala MK, Mizukami Y, Le LP, et al. Germline mutations in oncogene-induced senescence pathways are associated with multiple sessile serrated adenomas. Gastroenterology. 2014;146:520-529.
Egoavil C, Juarez M, Guarinos C, et al. Increased risk of colorectal cancer in patients with multiple serrated polyps and their first-degree relatives. Gastroenterology. 2017;153:106.e2-112.e2.
Edelstein DL, Cruz-Correa M, Soto-Salgado M, et al. Risk of colorectal and other cancers in patients with serrated polyposis. Clin Gastroenterol Hepatol. 2015;13:1697-1699.
He EY, Wyld L, Sloane MA, Canfell K, Ward RL. The molecular characteristics of colonic neoplasms in serrated polyposis: a systematic review and meta-analysis. J Pathol Clin Res. 2016;2:127-137.
Vos JR, Fakkert IE, Spruijt L, et al. Evaluation of yield and experiences of age-related molecular investigation for heritable and nonheritable causes of mismatch repair deficient colorectal cancer to identify Lynch syndrome. Int J Cancer. 2020;147:2150-2158.
Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet. 2009;76:1-18.
Cunningham JM, Christensen ER, Tester DJ, et al. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res. 1998;58:3455-3460.
Veigl ML, Kasturi L, Olechnowicz J, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci U S A. 1998;95:8698-8702.
Ladabaum U, Ford JM, Martel M, et al. American Gastroenterological Association technical review on the diagnosis and management of Lynch syndrome. Gastroenterology. 2015;149:783-813.
Moreira L, Munoz J, Cuatrecasas M, et al. Prevalence of somatic mutl homolog 1 promoter hypermethylation in Lynch syndrome colorectal cancer. Cancer. 2015;121:1395-1404.
Hampel H, Pearlman R, Beightol M, et al. Assessment of tumor sequencing as a replacement for Lynch syndrome screening and current molecular tests for patients with colorectal cancer. JAMA Oncol. 2018;4:806-813.
Sinicrope FA, Sargent DJ. Clinical implications of microsatellite instability in sporadic colon cancers. Curr Opin Oncol. 2009;21:369-373.
Schofield L, Watson N, Grieu F, et al. Population-based detection of Lynch syndrome in young colorectal cancer patients using microsatellite instability as the initial test. Int J Cancer. 2009;124:1097-1102.
Giraldez MD, Balaguer F, Bujanda L, et al. MSH6 and MUTYH deficiency is a frequent event in early-onset colorectal cancer. Clin Cancer Res. 2010;16:5402-5413.
Goshayeshi L, Ghaffarzadegan K, Khooei A, et al. Prevalence and clinicopathological characteristics of mismatch repair-deficient colorectal carcinoma in early onset cases as compared with late-onset cases: a retrospective cross-sectional study in Northeastern Iran. BMJ Open. 2018;8:e023102.

Auteurs

Hendrik Bläker (H)

Department of General Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany.

Saskia Haupt (S)

Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany.

Monika Morak (M)

Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Medical Genetics Center, Munich, Germany.

Elke Holinski-Feder (E)

Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Medical Genetics Center, Munich, Germany.

Alexander Arnold (A)

Department of General Pathology, Institute of Pathology, Charite Berlin, Berlin, Germany.

David Horst (D)

Department of General Pathology, Institute of Pathology, Charite Berlin, Berlin, Germany.

Julia Sieber-Frank (J)

Department of Applied Tumor Biology, University Hospital Heidelberg, Cooperation Unit Applied Tumor Biology, German Cancer research Center (DKFZ), and Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg, Heidelberg, Germany.

Florian Seidler (F)

Department of Applied Tumor Biology, University Hospital Heidelberg, Cooperation Unit Applied Tumor Biology, German Cancer research Center (DKFZ), and Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg, Heidelberg, Germany.

Moritz von Winterfeld (M)

Department of General Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.

Elizabeth Alwers (E)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Germany.

Jenny Chang-Claude (J)

Division of Cancer Epidemiology, Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ) Heidelberg, Hiedelberg, Germany.

Hermann Brenner (H)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Germany.
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT) Heidelberg, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Wilfried Roth (W)

Institute of Pathology, University Hospital Mainz, Mainz, Germany.

Christoph Engel (C)

Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.

Markus Löffler (M)

Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.

Gabriela Möslein (G)

Center for Hereditary Tumors, Helios University Hospital Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.

Hans-Konrad Schackert (HK)

Department of Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.

Jürgen Weitz (J)

Department of Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.

Claudia Perne (C)

Institute of Human Genetics, University of Bonn, Bonn, Germany.
Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.

Stefan Aretz (S)

Institute of Human Genetics, University of Bonn, Bonn, Germany.
Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.

Robert Hüneburg (R)

Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.

Wolff Schmiegel (W)

Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.

Deepak Vangala (D)

Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.

Nils Rahner (N)

Medical Faculty, Institute of Human Genetics, Heinrich-Heine University, Düsseldorf, Germany.

Verena Steinke-Lange (V)

Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
Medical Genetics Center, Munich, Germany.

Vincent Heuveline (V)

Engineering Mathematics and Computing Lab (EMCL), Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany.

Magnus von Knebel Doeberitz (M)

Department of Applied Tumor Biology, University Hospital Heidelberg, Cooperation Unit Applied Tumor Biology, German Cancer research Center (DKFZ), and Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg, Heidelberg, Germany.

Aysel Ahadova (A)

Department of Applied Tumor Biology, University Hospital Heidelberg, Cooperation Unit Applied Tumor Biology, German Cancer research Center (DKFZ), and Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg, Heidelberg, Germany.

Michael Hoffmeister (M)

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Germany.

Matthias Kloor (M)

Department of Applied Tumor Biology, University Hospital Heidelberg, Cooperation Unit Applied Tumor Biology, German Cancer research Center (DKFZ), and Molecular Medicine Partnership Unit (MMPU), University Hospital Heidelberg, Heidelberg, Germany.

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