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
Int J Colorectal Dis. 2019-10-26; 34(11): 1999-2002
DOI: 10.1007/s00384-019-03414-y

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1. Int J Colorectal Dis. 2019 Nov;34(11):1999-2002. doi: 10.1007/s00384-019-03414-y.
Epub 2019 Oct 26.

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

Pirini F(1), Tedaldi G(2), Danesi R(3), Cangini I(2), Tumedei MM(2), Ferrari
A(2), Vitali S(4), De Maio G(2), Terragna C(5), Solli V(5), Tebaldi M(2),
Puccetti M(6), Zampiga V(2), Ravegnani M(3), Ulivi P(2), Falcini F(3), Martinelli
G(7), Calistri D(2).

Author information:
(1)Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura
dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.
.
(2)Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura
dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.
(3)Romagna Cancer Registry, Istituto Scientifico Romagnolo per lo Studio e la
Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
(4)Department of Physics and Astronomy, University of Bologna, Bologna, Italy.
(5)L. & A. Seragnoli Institute of Haematology, Bologna University School of
Medicine, Bologna, Italy.
(6)Azienda Unità Sanitaria Locale (AUSL) Imola, Imola, Italy.
(7)Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e
la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

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.

DOI: 10.1007/s00384-019-03414-y
PMID: 31655866 [Indexed for MEDLINE]

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