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First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer

Gianluca Tedaldi1*, Rita Danesi1, Valentina Zampiga1, Michela Tebaldi1, Lucia Bedei2, Wainer Zoli1, Dino Amadori1, Fabio Falcini1 and Daniele Calistri1

Author Affiliations

1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

2 Cancer Prevention Unit, Morgagni-Pierantoni Hospital, Forlì, Italy

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BMC Cancer 2014, 14:478  doi:10.1186/1471-2407-14-478

Published: 1 July 2014



CHEK2 is a multi-cancer susceptibility gene whose common germline mutations are known to contribute to the risk of developing breast and prostate cancer.

Case presentation

Here, we describe an Italian family with a high number of cases of breast cancer and other types of tumour subjected to the MLPA test to verify the presence of BRCA1, BRCA2 and CHEK2 deletions and duplications. We identified a new 23-kb duplication in the CHEK2 gene extending from intron 5 to 13 that was associated with breast cancer in the family. The presence and localisation of the alteration was confirmed by a second analysis by Next-Generation Sequencing.


This finding suggests that CHEK2 mutations are heterogeneous and that techniques other than sequencing, such as MLPA, are needed to identify CHEK2 mutations. It also indicates that CHEK2 rare variants, such as duplications, can confer a high susceptibility to cancer development and should thus be studied in depth as most of our knowledge of CHEK2 concerns common mutations.

CHEK2; Duplication; Breast cancer; Hereditary cancer; MLPA; Next-generation sequencing