Familial Cancer

, Volume 16, Issue 1, pp 1–16 | Cite as

Characterization of BRCA1 and BRCA2 variants found in a Norwegian breast or ovarian cancer cohort

  • Elisabeth Jarhelle
  • Hilde Monica Frostad Riise Stensland
  • Lovise Mæhle
  • Marijke Van Ghelue
Original Article


Germline mutations in BRCA1 and BRCA2 cause hereditary breast and ovarian cancer. Molecular screening of these two genes in patients with a family history of breast or ovarian cancer has revealed pathogenic variants as well as genetic variants of unknown significance (VUS). These VUS may cause a challenge in the genetic counseling process regarding clinical management of the patient and the family. We investigated 32 variants previously detected in 33 samples from patients with a family history of breast or ovarian cancer. cDNA was analyzed for alternative transcripts and selected missense variants located in the BRCT domains of BRCA1 were assessed for their trans-activation ability. Although an extensive cDNA analysis was done, only three of the 32 variants appeared to affect the splice-process (BRCA1 c.213-5T>A, BRCA1 c.5434C>G and BRCA2 c.68-7T>A). In addition, two variants located in the BRCT domains of BRCA1 (c.5075A>C p.Asp1692Ala and c.5513T>G p.Val1838Gly) were shown to abolish the BRCT domain trans-activation ability, whereas BRCA1 c.5125G>A p.Gly1709Arg exhibited equal trans-activation capability as the WT domain. These functional studies may offer further insights into the pathogenicity of certain identified variants; however, this assay is only applicable for a subset of missense variants.


BRCA1 BRCA2 Cancer cDNA-analysis Functional-assay 



We thank Alvaro N. A. Monteiro for kindly providing us with the BRCT containing plasmids necessary for the trans-activation assay. We also thank “Helse Nord” for providing the necessary funding for this study (Grant # SFP1161-14).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

All participants gave written informed consent for diagnostic testing. The project was submitted to the appropriate regional ethics committee, however, since the samples were tested diagnostically the regional ethical committee waved the need for ethical approval based on the Norwegian regional health organization law § 2 and § 9 and the Norwegian research ethical law § 4.


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Medical Genetics, Division of Child and Adolescent HealthUniversity Hospital of North NorwayTromsøNorway
  2. 2.Department of Clinical MedicineUniversity of TromsøTromsøNorway
  3. 3.Northern Norway Family Cancer CenterUniversity Hospital of North NorwayTromsøNorway
  4. 4.Department of Medical GeneticsOslo University HospitalOsloNorway

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