N14: Identification And Characterization Of An Alu Element Insertion In BRCA2 In A Spanish Family Associated To Prostate Cancer

V. Barca-Tierno1, M. Morín1, L. Santos1, C García-Hoz3, L. Fuente-García1, P. Marcos-Cava1, M. Salazar2, C. Guillén-Ponce2, M. A. Moreno-Pelayo1

1 – Genetics Service. Ramon and Cajal Hospital-IRYCIS-CIBERER.Raregenomics. 2 – Oncology Service. Ramon and Cajal Hospital. 3 – Immunology Service. Ramon and Cajal Hospital.


Aim: Pathogenic Alu element insertions are rarely reported because this type of insertions are undetectable with the classical screening methods. The aim of this work has been the identification and characterization of an Alu element insertion in a Spanish family with a history of breast/ovarian cancer.

Method: Molecular analysis was carried out using the BRCA MASTRDx (Multiplicom) and Massively Parallel Sequencing (Illumina). The Alu insertion was identified and characterized by fragments analysis, genotyping, PCR amplification and Sanger sequencing (ABI3130).

Results: We have identified and characterized a heterozygous pathogenic variant c.5007_5008ins174 located at the exon 11 of the BRCA2 gene in a patient with prostate cancer. The variant identified is a pathogenic Alu element insertion (AluYb8BRCA2) of about 174 bp long.

Conclusion: NGS has been incorporated into clinical genetic testing for hereditary cancer risk. NGS-based techniques and the standard bioinformatic pipelines, however, are unable to detect and precissely characterize ALU element insertions. In this work, we report, by using classical screening methods and bioinformatic programs, BLAST and RepeatMasked, the identification of the AluYb8BRCA2 insertion in BRCA2 coding region. This insertion could generate a framesift resulting in the abrogation of BRCA2 protein function that has been associated with oxidative stress involved in carcinogenesis.