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Signatures of rearrangement processes in whole genome sequences of breast cancers

Dominik Glodzik, Lund University 
Dominik Glodzik, Lund University 
Speaker Name: 
Dominik Glodzik 
Speaker Title: 
Assistant Researcher
Speaker Organization: 
Lund University
Start Time: 
Tuesday, April 11, 2017 - 11:15am
End Time: 
Tuesday, April 11, 2017 - 12:15pm
599 Engineering 2
Benedict Paten



Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Whole genome sequences reveal structural variation in full detail. In this talk I will describe our studies on origin and consequences of rearrangements in breast cancer genomes.

Firstly, we characterized the types of rearrangements often seen in across patients. Our mathematical analysis of common rearrangement patterns revealed six signatures of rearrangement processes. Two particular rearrangement signatures are abundant in samples of patients with germline mutations in BRCA1 and BRCA2 genes, whose DNA repair through homologous recombination is compromised. The origin of other recurrent rearrangement signatures is still to be discovered.

Secondly, I will discuss possible consequences of somatic rearrangements for cancer initiation and progression. We systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci and breast-specific ‘super-enhancer’ regulatory elements. We thus present a somatic-rearrangement mutational process affecting coding sequences and noncoding regulatory elements and contributing a continuum of driver consequences.

Hosted by Benedict Paten