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

BMC Cancer

Gianluca Tedaldi²  Rita Danesi²  Valentina Zampiga²  Michela Tebaldi²  Lucia Bedei¹  Wainer Zoli²  Dino Amadori²  Fabio Falcini²  Daniele Calistri² 

[1] Cancer Prevention Unit, Morgagni-Pierantoni Hospital, Forlì, Italy

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

关键词: Next-generation sequencing;    MLPA;    Hereditary cancer;    Breast cancer;    Duplication;    CHEK2;   

Others  :  855332
DOI  :  10.1186/1471-2407-14-478

 received in 2013-10-29, accepted in 2014-06-25,  发布年份 2014

【 摘 要 】

Background

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.

Conclusions

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.

【 授权许可】

   
2014 Tedaldi et al.; licensee BioMed Central Ltd.

【 图 表 】

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