2020
DOI: 10.1002/ijc.33273
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Age‐dependent performance of BRAF mutation testing in Lynch syndrome diagnostics

Abstract: 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… Show more

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Cited by 23 publications
(9 citation statements)
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“…Patients [71]. Presence of MLH1 promoter methylation can also exclude LS patients from screening pipelines, either as the second hit in MLH1, which occurs in 15.8% (3/19; 95% CI: 3.4-39.6%) of CRCs arising in pathogenic MLH1 variant carriers [72], or as a germline MLH1 epimutation, which accounts for 2-3% of MLH1-asscociated LS [73][74][75].…”
Section: Not All Colorectal Cancers Are Made Equalmentioning
confidence: 99%
“…Patients [71]. Presence of MLH1 promoter methylation can also exclude LS patients from screening pipelines, either as the second hit in MLH1, which occurs in 15.8% (3/19; 95% CI: 3.4-39.6%) of CRCs arising in pathogenic MLH1 variant carriers [72], or as a germline MLH1 epimutation, which accounts for 2-3% of MLH1-asscociated LS [73][74][75].…”
Section: Not All Colorectal Cancers Are Made Equalmentioning
confidence: 99%
“…Furthermore, it is important to note that approximately 70% of methylated tumors exhibit BRAF p.V600E mutations, which serve as a surrogate marker for MLH1 promoter methylation. Patients with LS may have somatic BRAF p.V600E mutations present in their tumors [ 20 ] which can render them ineligible for germline sequencing. Similarly, the occurrence of hypermethylation in the MLH1 promoter could arise as a second hit in LS patients who possess pathogenic MLH1 variants.…”
Section: Discussionmentioning
confidence: 99%
“…However, it is important to note that MSP has limitations in detecting LS in certain cases – as approximately 6.9% of LS-associated CRC may appear to have proficient MMR expression based on IHC or MSI analysis [ 18 ]. Moreover, MLH1 promoter hypermethylation or the BRAF p.V600E mutation, which typically exclude patients from germline sequencing in MSP, can arise as a second hit in LS patients carrying pathogenic MLH1 variants [ 19 20 21 ]. Immediate germline sequencing (IGS), which involves the analysis of MMR genes irrespective of MMR deficiency status, could theoretically offer greater sensitivity in comparison to MSP.…”
Section: Introductionmentioning
confidence: 99%
“…Zusätzlich weisen diese Tumoren eine Assoziation zu BRAF-Mutationen auf. Diese treten bei LS-Patienten hingegen äußerst selten auf und dann meist nur in jüngerem Alter [30].…”
Section: Dmmr/msi-high Und Immunogenitätunclassified