జర్నల్ ఆఫ్ డేటా మైనింగ్ ఇన్ జెనోమిక్స్ & ప్రోటీమిక్స్

నైరూప్య

Whole Exome Sequencing Reveals a Combination of Rare High and Low Penetrance Variants that Correlate with Familial Breast Cancer Relative Risk

Ben Rekaya Mariem, Hamdi Yosr, El Benna Houda, Mejri Nessrine, Jaidane Olfa, Ayari Jihene, Ben Nasr Sonia, Dallali Hamza, Messaoud Olfa, Meddeb Rym, Mighri Najah, Boujemaa Maroua, Boubaker Mohamed Samir, Haddaoui Abderazek, Mrad Ridha, Boussen Hamouda, Abdelhak Sonia, Labidi Soumaya1

Objective: We aimed to investigate and identify simultaneously all rare pathogenic and common variants in unrelated Breast Cancer (BC) cases.

Methods: All frequent mutations in BRCA genes previously identified in Tunisia have been excluded by Sanger sequencing in 42 women affected with high family risk having at least 3 cancer affected related individuals. Two unrelated cases having two different family histories have been selected for whole exome sequencing. Selected high risk variants were confirmed and segregation analysis was performed.

Results: We identified a pathogenic frame-shift loss of function variant in BRCA2 p.Val1283Lysfs in three cases and a pathogenic rare variant in OGG1, p.Arg46Gln that co-segregates with a rare non sense variant in BRCA2, p.K3326X, in two breast cancer affected cases. These variants have never been described in Tunisia or North Africa.

Conclusion: Family history and the young age at onset for patient F1.1 correlate with the presence of a high penetrant variant (p.Val1283Lysfs) in BRCA2 gene. However, the late age at onset and the less severe phenotype for patient F2.2 are the consequence of the presence of a low penetrant variant Lys3326X in BRCA2 that co-segregate with a pathogenic variant p.Arg46Gln in OGG1 gene only in BC cases.