title: First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. gianluca.tedaldi@irst.emr.it.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tedaldi
authors.forename: Rita
authors.initials: R
authors.lastname: Danesi
authors.forename: Valentina
authors.initials: V
authors.lastname: Zampiga
authors.forename: Michela
authors.initials: M
authors.lastname: Tebaldi
authors.forename: Lucia
authors.initials: L
authors.lastname: Bedei
authors.forename: Wainer
authors.initials: W
authors.lastname: Zoli
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Fabio
authors.initials: F
authors.lastname: Falcini
authors.forename: Daniele
authors.initials: D
authors.lastname: Calistri
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D007558:Italy; D008875:Middle Aged; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human