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Familial Cancer

, Volume 14, Issue 1, pp 77–80 | Cite as

MLH1 promotor hypermethylation does not rule out a diagnosis of Lynch syndrome: a case report

  • Victoria M. RaymondEmail author
  • Arden M. Morris
  • Khaled S. Hafez
  • Joel K. Greenson
Short Communication

Abstract

There are approximately 136,830 new colorectal cancer (CRC) cases diagnosed annually in the United States. In an effort to identify those at highest risk for Lynch Syndrome, an inherited CRC predisposition syndrome, several professional guidelines advocate for routine screening of all colorectal adenocarcinomas for features of DNA mismatch repair, microsatellite instability (MSI) and/or absent immunohistochemistry staining. Approximately 12–17 % of CRCs demonstrate MSI with germline mutations in genes involved in DNA mismatch repair, MLH1, MSH2, MSH6, PMS2 and TACSTD1/EPCAM and somatic MLH1 promotor hypermethylation being alternative pathways for the development of microsatellite unstable CRC. It is important to distinguish between these two events as the underlying cause of cancer development as management and implications for the patient and family members vary significantly. We describe a patient with multiple primary cancers, a deleterious germline MSH6 mutation and somatic MLH1 promotor hypermethylation highlighting the importance of incorporating the clinical history with the genetic evaluation.

Keywords

Lynch syndrome MLH1 promotor hypermethylation Genetic testing Colorectal cancer 

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Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Victoria M. Raymond
    • 1
    Email author
  • Arden M. Morris
    • 2
  • Khaled S. Hafez
    • 3
  • Joel K. Greenson
    • 4
  1. 1.Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Department of SurgeryUniversity of MichiganAnn ArborUSA
  3. 3.Department of UrologyUniversity of MichiganAnn ArborUSA
  4. 4.Department of PathologyUniversity of MichiganAnn ArborUSA

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