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

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• 作者：Gianluca Tedaldi (24)
  Rita Danesi (24)
  Valentina Zampiga (24)
  Michela Tebaldi (24)
  Lucia Bedei (25)
  Wainer Zoli (24)
  Dino Amadori (24)
  Fabio Falcini (24)
  Daniele Calistri (24)
  
  24. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS ; Meldola ; Italy
  25. Cancer Prevention Unit ; Morgagni-Pierantoni Hospital ; Forl矛 ; Italy
  
• 关键词：CHEK2 ; Duplication ; Breast cancer ; Hereditary cancer ; MLPA ; Next ; generation sequencing
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：706 KB
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  23. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/478/prepub
  
• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

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.