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MLH1 Hypermethylation/BRAF Mutation
Clinical Genetic Test
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offered by
Mayo Clinic Laboratories
View lab's test page
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GTR Test Accession: Help GTR000597580.2
CANCERDIGESTIVE SYSTEM
Last updated in GTR: 2024-03-25
View version history
Last annual review date for the lab: 2023-05-30 LinkOut
At a Glance
Test purpose: Help
Prognostic; Screening; Therapeutic management
Conditions (1): Help
Colon cancer
Genes (2): Help
BRAF (7q34), MLH1 (3p22.2)
Methods (1): Help
Molecular Genetics - Methylation analysis: Methylation-specific PCR
Target population: Help
An adjunct to MSI / Microsatellite Instability (MSI), Tumor and …
Clinical validity: Help
Not provided
Clinical utility: Help
Guidance for management
Ordering Information
Offered by: Help
Mayo Clinic Laboratories
View lab's website
View lab's test page
Test short name: Help
BRMLH
Specimen Source: Help
Who can order: Help
  • Genetic Counselor
  • Health Care Provider
  • Licensed Dentist
  • Licensed Physician
  • Nurse Practitioner
  • Physician Assistant
  • Public Health Mandate
  • Registered Nurse
Test Order Code: Help
BRMLH
View other test codes
LOINC codes: Help
**LOINC codes notice
CPT codes: Help
**AMA CPT codes notice

Copyright: 2023 American Medical Association. All rights reserved.

Lab contact: Help
Megan Hoenig, MS, MPH, Certified Genetic counselor, CGC, Genetic Counselor
GCMolgen@mayo.edu
1-800-533-1710
Contact Policy: Help
Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.
How to Order: Help
https://www.mayocliniclabs.com/test-catalog/overview/35491#Specimen
Order URL
Test development: Help
Test developed by laboratory (no manufacturer test name)
Informed consent required: Help
Based on applicable state law
Pre-test genetic counseling required: Help
Decline to answer
Post-test genetic counseling required: Help
Decline to answer
Recommended fields not provided:
Test strategy
Conditions Help
Total conditions: 1
Condition/Phenotype Identifier
Test Targets
Genes Help
Total genes: 2
Gene Associated Condition Germline or Somatic Allele (Lab-provided) Variant in NCBI
Methodology
Total methods: 1
Method Category Help
Test method Help
Instrument *
Methylation analysis
Methylation-specific PCR
* Instrument: Not provided
Clinical Information
Test purpose: Help
Prognostic; Screening; Therapeutic management
Clinical utility: Help
Guidance for management
View citations (1)
  • NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019. Gupta S, et al. J Natl Compr Canc Netw. 2019;17(9):1032-1041. doi:10.6004/jnccn.2019.0044. PMID: 31487681.

Target population: Help
An adjunct to MSI / Microsatellite Instability (MSI), Tumor and IHC / Mismatch Repair (MMR) Protein Immunohistochemistry Only, Tumor testing, when colon tumor demonstrates microsatellite instability (MSI-H) and loss of MLH1 protein expression, to help distinguish a somatic versus germline event prior to performing expensive germline testing. An adjunct to … View more
View citations (5)
  • Cunningham JM, Kim CY, Christensen ER, Tester DJ, Parc Y, Burgart LJ, Halling KC, McDonnell SK, Schaid DJ, Walsh Vockley C, Kubly V, Nelson H, Michels VV, Thibodeau SN. The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet. 2001;69(4):780-90. doi:10.1086/323658. Epub 2001 Aug 24. PMID: 11524701.
  • BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Wang L, et al. Cancer Res. 2003;63(17):5209-12. PMID: 14500346.
  • BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. Domingo E, et al. J Med Genet. 2004;41(9):664-8. doi:10.1136/jmg.2004.020651. PMID: 15342696.
  • Distinction of hereditary nonpolyposis colorectal cancer and sporadic microsatellite-unstable colorectal cancer through quantification of MLH1 methylation by real-time PCR. Bettstetter M, et al. Clin Cancer Res. 2007;13(11):3221-8. doi:10.1158/1078-0432.CCR-06-3064. PMID: 17545526.
  • NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019. Gupta S, et al. J Natl Compr Canc Netw. 2019;17(9):1032-1041. doi:10.6004/jnccn.2019.0044. PMID: 31487681.
Research:
Is research allowed on the sample after clinical testing is complete? Help
Research testing is only performed under IRB approved protocol with an opt-out policy in place.
Recommended fields not provided:
Clinical validity, What is the protocol for interpreting a variation as a VUS?, Are family members with defined clinical status recruited to assess significance of VUS without charge?, Will the lab re-contact the ordering physician if variant interpretation changes?, Sample negative report, Sample positive report
Technical Information
Test Procedure: Help
A methylation-specific polymerase chain reaction (PCR)-based assay is used to test tumor DNA for the presence of hypermethylation of the MLH1 promoter, based on a modification of the method described by Grady et al (Grady WM, Rajput A, Lutterbaugh JD, Markowitz S: Detection of aberrantly methylated hMLH1 promoter DNA in … View more
Availability: Help
Tests performed
Entire test performed in-house
Analytical Validity: Help
A total of 108 FFPE cases were run for accuracy for the ML1HM portion of this test. Of the 108 cases there was 100% concordance with the refence result. The limit of detection for the presence of MLH1 promoter methylation was determined to be 10% tumor. A total of 86 … View more
Assay limitations: Help
Testing tumors other than colon (in the evaluation of Lynch syndrome) for BRAF and MLH1 hypermethylation has not been fully evaluated; therefore, other specimens are not accepted. Colon cancer is relatively common and it is possible for a sporadic colon cancer to occur in a Lynch syndrome family. Therefore, evaluation … View more
Proficiency testing (PT):
Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Alternative Assessment

PT Provider: Help
Platform PT covered utilizing ML1HM assay

Description of PT method: Help
Platform PT covered utilizing ML1HM assay
Recommended fields not provided:
Test Confirmation, Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, Major CAP category, CAP category, CAP test list
Regulatory Approval
FDA Review: Help
Category: FDA exercises enforcement discretion
Additional Information
Practice guidelines:
Consumer resources:

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.