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Familial Cancer

, Volume 17, Issue 2, pp 281–285 | Cite as

Sporadic endometrial adenocarcinoma with MMR deficiency due to biallelic MSH2 somatic mutations

  • Bruno Buecher
  • Antoine De Pauw
  • Louis Bazire
  • Claude Houdayer
  • Alice Fievet
  • Virginie Moncoutier
  • Fereshteh Farkhondeh
  • Samia Melaabi
  • Dominique Stoppa Lyonnet
  • Lisa Golmard
Short Communication

Abstract

The invalidation of the Mismatch Repair (MMR) system is responsible for a so-called “deficient MMR” phenotype (dMMR) characterized by microsatellite instability and abnormal pattern of expression of MMR proteins in tumor tissue. This phenotype occurs in at least 20% of sporadic endometrial adenocarcinomas by epigenetic silencing of MLH1 gene. It is also observed in virtually all tumors occurring in patients with Lynch syndrome by monoallelic germline mutation in one of the MMR genes. The determination of this phenotype (dMMR vs. proficient MMR—pMMR) has therefore a pivotal place in the diagnosis algorithm for Lynch syndrome by monoallelic germline mutation in one of the MMR genes. The determination of this phenotype (dMMR vs. proficient MMR—pMMR) has therefore a pivotal place in the diagnosis algorithm for Lynch syndrome. We report the case of a woman with an early-onset endometrial adenocarcinoma who was suspected to be affected with Lynch syndrome based on tumor dMMR phenotype (MSI associated with loss of expression of MSH2 and MSH6 proteins). After complete germline and somatic evaluations, this phenotype was eventually explained by two MSH2 somatic mutations and the diagnosis of Lynch-like syndrome due to an unidentified MSH2 germline mutation was ruled out. Somatic mosaicism at low mutation rate was unlikely as no mutation was detected by DNA analysis from various tissue samples. Nevertheless, the three patient’s children were tested for the two mutations and these tests were negative. Biallelic somatic mutations of one MMR gene is a mechanism of invalidation of the MMR system in sporadic cases. Clinicians have to be aware of this mechanism because of the great clinical implication for the patients and their relatives.

Keywords

Endometrial adenocarcinoma Deficient MMR phenotype MMR genes somatic mutations 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Bruno Buecher
    • 1
  • Antoine De Pauw
    • 1
  • Louis Bazire
    • 2
  • Claude Houdayer
    • 1
  • Alice Fievet
    • 1
  • Virginie Moncoutier
    • 1
  • Fereshteh Farkhondeh
    • 3
  • Samia Melaabi
    • 1
  • Dominique Stoppa Lyonnet
    • 1
  • Lisa Golmard
    • 1
  1. 1.Department of GeneticsInstitut CurieParis Cedex 05France
  2. 2.Department of RadiotherapyInstitut CurieParis Cedex 05France
  3. 3.Department of PathologyInstitut CurieParis Cedex 05France

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