Type

Journal Article

Authors

Adrian P Bracken
James G Geraghty
Daniel G Bradley
Andrew J Green
Elaine Kenny
Marie Meany
Nuala Cody
Chris M Egan
Russell Mclaughlin
Jonah McGreevy
and 3 others

Subjects

Medicine & Nursing

Topics
families breast cancer susceptibility genetics brca1 ireland detection breast cancer next generation sequencing

Detection of novel germline mutations for breast cancer in non-BRCA1/2 families. (2015)

Abstract The identification of the breast cancer susceptibility genes BRCA1 and BRCA2 enhanced clinicians' ability to select high-risk individuals for aggressive surveillance and prevention, and led to the development of targeted therapies. However, BRCA1/2 mutations account for only 25% of familial breast cancer cases. To systematically identify rare, probably pathogenic variants in familial cases of breast cancer without BRCA1/2 mutations, we developed a list of 312 genes, and performed targeted DNA enrichment coupled to multiplex next-generation sequencing on 104 'BRCAx' patients and 101 geographically matched controls in Ireland. As expected, this strategy allowed us to identify mutations in several well-known high-susceptibility and moderate-susceptibility genes, including ATM (~ 5%), RAD50 (~ 3%), CHEK2 (~ 2%), TP53 (~ 1%), PALB2 (~ 1%), and MRE11A (~ 1%). However, we also identified novel pathogenic variants in 30 other genes, which, when taken together, potentially explain the etiology of the missing heritability in up to 35% of BRCAx patients. These included novel potential pathogenic mutations in MAP3K1, CASP8, RAD51B, ZNF217, CDKN2B-AS1, and ERBB2, including a splice site mutation, which we predict would generate a constitutively active HER2 protein. Taken together, this work extends our understanding of the genetics of familial breast cancer, and supports the need to implement hereditary multigene panel testing to more appropriately orientate clinical management.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Adrian P Bracken, James G Geraghty, Daniel G Bradley, Andrew J Green, Elaine Kenny, Marie Meany, Nuala Cody, Chris M Egan, Russell Mclaughlin, Jonah McGreevy and 3 others

Experts in our system

1
Adrian Bracken
Trinity College Dublin
Total Publications: 24
 
2
James Geraghty
Trinity College Dublin
Total Publications: 5
 
3
Daniel Bradley
Trinity College Dublin
Total Publications: 76
 
4
Andrew Green
Trinity College Dublin
Total Publications: 25
 
5
Elaine Kenny
Trinity College Dublin
Total Publications: 28
 
6
Chris M Egan
Trinity College Dublin
Total Publications: 5
 
7
Russell L McLaughlin
Trinity College Dublin
Total Publications: 39