Skip to Main content Skip to Navigation
Journal articles

Germline copy number variations in BRCA1/2 negative families: Role in the molecular etiology of hereditary breast cancer in Tunisia

Abstract : Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APO-BECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes.
Document type :
Journal articles
Complete list of metadata
Contributor : AbdelHakim Ben Hassine Connect in order to contact the contributor
Submitted on : Monday, January 24, 2022 - 1:41:16 PM
Last modification on : Monday, January 24, 2022 - 6:14:29 PM
Long-term archiving on: : Monday, April 25, 2022 - 7:10:45 PM


Publication funded by an institution


Distributed under a Creative Commons Attribution 4.0 International License




Maroua Boujemaa, Yosr Hamdi, Nesrine Mejri, Lilia Romdhane, Kais Ghedira, et al.. Germline copy number variations in BRCA1/2 negative families: Role in the molecular etiology of hereditary breast cancer in Tunisia. PLoS ONE, Public Library of Science, 2021, 16 (1), pp.e0245362. ⟨10.1371/journal.pone.0245362⟩. ⟨pasteur-03541051⟩



Record views


Files downloads