Identification of a novel large EPCAM-MSH2 duplication, concurrently with LOHs in chromosome 20 and X, in a family with Lynch syndrome

Francesca Pirini, Gianluca Tedaldi, Rita Danesi, Ilaria Cangini, Maria Maddalena Tumedei, Anna Ferrari, Silvia Vitali, Giulia De Maio, Carolina Terragna, Vincenza Solli, Michela Tebaldi, Maurizio Puccetti, Valentina Zampiga, Mila Ravegnani, Paola Ulivi, Fabio Falcini, Giovanni Martinelli, Daniele Calistri

Research output: Contribution to journalArticlepeer-review


Background: Lynch syndrome (LS) is associated with germline mutations in one of the mismatch repair genes or EPCAM. The majority of the causative alterations are point mutations. Large genomic rearrangements represent only 5–20%. Hypothetically, the allelic imbalance, like the loss of heterozygosity, may be another high penetrance risk factor. Case presentation: We describe the case of a patient who developed 5 tumors during her lifetime and with a family history characterized by a high frequency of tumors associated with LS. The proband was tested for mutations and copy number alterations with a panel of hereditary cancer genes and by SNP array. She showed a 187 Kb duplication including EPCAM and the first 7 exons of MSH2, plus two loss of heterozygosity (LOHs) in chromosome 20 and one in chromosome X which include many tumor suppressor genes. Conclusion: We found a novel large EPCAM-MSH2 duplication associated with LS and the presence of LOHs in regions containing numerous tumor suppressors, raising the hypothesis that these alterations could contribute to cancer susceptibility. Our results underline the importance to deepen the knowledge of molecular mechanisms in order to determine the role in cancer predisposition of novel genetic alterations.

Original languageEnglish
Pages (from-to)1999-2002
Number of pages4
JournalInternational Journal of Colorectal Disease
Issue number11
Publication statusPublished - Nov 1 2019


  • EPCAM-MSH2 duplication
  • Loss of heterozygosity
  • Lynch syndrome
  • Multiple gene panel
  • Next-generation sequencing

ASJC Scopus subject areas

  • Gastroenterology

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