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

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

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

Hendrik Bläker 1, Saskia Haupt 2, Monika Morak 3 4, Elke Holinski-Feder 3 4, Alexander Arnold 5, David Horst 5, Julia Sieber-Frank 6, Florian Seidler 6, Moritz von Winterfeld 7, Elizabeth Alwers 8, Jenny Chang-Claude 9, Hermann Brenner 8 10 11, Wilfried Roth 12, Christoph Engel 13, Markus Löffler 13, Gabriela Möslein 14, Hans-Konrad Schackert 15, Jürgen Weitz 15, Claudia Perne 16 17, Stefan Aretz 16 17, Robert Hüneburg 17, Wolff Schmiegel 18, Deepak Vangala 18, Nils Rahner 19, Verena Steinke-Lange 3 4, Vincent Heuveline 2, Magnus von Knebel Doeberitz 6, Aysel Ahadova 6, Michael Hoffmeister 8, Matthias Kloor 6, German Consortium for Familial Intestinal Cancer

Affiliations 

• PMID: 32875553
 
• DOI: 10.1002/ijc.33273

Abstract

BRAF V600E mutations have been reported as a marker of sporadic microsatellite-unstable (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. 6/7 LS patients with BRAF-mutant CRC and reported age were < 50 years. Among 339/756 (44.8%) of BRAF mutations detected in unselected MSI CRC, only 2/339 (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 counselling without BRAF testing. This article is protected by copyright. All rights reserved.

Keywords: BRAF mutation testing; Lynch syndrome diagnostics; age; hereditary cancer syndrome; microsatellite-unstable colorectal cancer.

This article is protected by copyright. All rights reserved.

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