Novel BRCA1 splice-site mutation in ovarian cancer patients of Slavic origin
- 176 Downloads
Mutations in breast cancer susceptibility gene 1 (BRCA1) lead to defects in a number of cellular pathways including DNA damage repair and transcriptional regulation, resulting in the elevated genome instability and predisposing to breast and ovarian cancers. We report a novel mutation LRG_292t1:c.4356delA,p.(Ala1453Glnfs*3) in the 12th exon of BRCA1, in the splice site region near the donor site of intron 12. It is a frameshift mutation with the termination codon generated on the third amino acid position from the site of deletion. Human Splice Finder 3.0 and MutationTaster have assessed this variation as disease causing, based on the alteration of splicing, creation of premature stop codon and other potential alterations initiated by nucleotide deletion. Among the most important alterations are frameshift and splice site changes (score of the newly created donor splice site: 0.82). c.4356delA was associated with two ovarian cancer cases in two families of Slavic origin. It was detected by next generation sequencing, and confirmed with Sanger sequencing in both cases. Because of the fact that it changes the reading frame of the protein, novel mutation c.4356delA p.(Ala1453Glnfs*3) in BRCA1 gene might be of clinical significance for hereditary ovarian cancer. Further functional as well as segregation analyses within the families are necessary for appropriate clinical classification of this variant. Since it has been detected in two ovarian cancer patients of Slavic origin, it is worth investigating founder effect of this mutation in Slavic populations.
KeywordsBRCA1 Novel mutation Ovarian cancer Slavic populations
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 15.National Guidelines of Good Clinical Practice: Breast Cancer Diagnosis and Treatment (Serbian) (2013) Ed. Radan Dzodic, Ministry of Health of Republic of SerbiaGoogle Scholar
- 24.Kohlmann W, Gruber SB (1993) Lynch syndrome. University of Washington, SeattleGoogle Scholar
- 27.Gatei M, Zhou B-B, Hobson K et al (2001) Ataxia Telangiectasia Mutated (ATM) Kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites: IN VIVO ASSESSMENT USING PHOSPHO-SPECIFIC ANTIBODIES. J Biol Chem 276:17276–17280. doi: 10.1074/jbc.M011681200 CrossRefPubMedGoogle Scholar