Email updates

Keep up to date with the latest news and content from BMC Medical Genomics and BioMed Central.

Open Access Highly Accessed Research article

Identification of gene fusion transcripts by transcriptome sequencing in BRCA1-mutated breast cancers and cell lines

Kevin CH Ha12, Emilie Lalonde12, Lili Li134, Luca Cavallone34, Rachael Natrajan5, Maryou B Lambros5, Costas Mitsopoulos5, Jarle Hakas5, Iwanka Kozarewa5, Kerry Fenwick5, Chris J Lord5, Alan Ashworth5, Anne Vincent-Salomon6, Mark Basik478, Jorge S Reis-Filho5, Jacek Majewski12 and William D Foulkes1347*

Author affiliations

1 Department of Human Genetics, McGill University, Room N5-13, Stewart Biology Building, 1205 Dr. Penfield Ave, Montreal, Quebec, H3A 1B1, Canada

2 McGill University and Genome Quebec Innovation Centre, 740 Dr. Penfield Ave, Montreal, Quebec, H3A 1A4, Canada

3 Program in Cancer Genetics, McGill University, 546 Pine Ave, Montreal, Quebec, H2W 1S6, Canada

4 Segal Cancer Centre, Lady Davis Institute, Jewish General Hospital, 3755 Côte-Ste-Catherine Road, Montreal, Quebec, H3T 1E2, Canada

5 The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

6 Institut Curie, 26 Rue d'Ulm, 75248, Paris, France

7 Department of Oncology, Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, H3T 1E2, Canada

8 Department of Surgery, Lady Davis Institute, Jewish General Hospital, McGill University, 3755 Côte-Ste-Catherine Road, Montreal, Quebec, H3T 1E2, Canada

For all author emails, please log on.

Citation and License

BMC Medical Genomics 2011, 4:75  doi:10.1186/1755-8794-4-75

Published: 27 October 2011



Gene fusions arising from chromosomal translocations have been implicated in cancer. However, the role of gene fusions in BRCA1-related breast cancers is not well understood. Mutations in BRCA1 are associated with an increased risk for breast cancer (up to 80% lifetime risk) and ovarian cancer (up to 50%). We sought to identify putative gene fusions in the transcriptomes of these cancers using high-throughput RNA sequencing (RNA-Seq).


We used Illumina sequencing technology to sequence the transcriptomes of five BRCA1-mutated breast cancer cell lines, three BRCA1-mutated primary tumors, two secretory breast cancer primary tumors and one non-tumorigenic breast epithelial cell line. Using a bioinformatics approach, our initial attempt at discovering putative gene fusions relied on analyzing single-end reads and identifying reads that aligned across exons of two different genes. Subsequently, latter samples were sequenced with paired-end reads and at longer cycles (producing longer reads). We then refined our approach by identifying misaligned paired reads, which may flank a putative gene fusion junction.


As a proof of concept, we were able to identify two previously characterized gene fusions in our samples using both single-end and paired-end approaches. In addition, we identified three novel in-frame fusions, but none were recurrent. Two of the candidates, WWC1-ADRBK2 in HCC3153 cell line and ADNP-C20orf132 in a primary tumor, were confirmed by Sanger sequencing and RT-PCR. RNA-Seq expression profiling of these two fusions showed a distinct overexpression of the 3' partner genes, suggesting that its expression may be under the control of the 5' partner gene's regulatory elements.


In this study, we used both single-end and paired-end sequencing strategies to discover gene fusions in breast cancer transcriptomes with BRCA1 mutations. We found that the use of paired-end reads is an effective tool for transcriptome profiling of gene fusions. Our findings suggest that while gene fusions are present in some BRCA1-mutated breast cancers, they are infrequent and not recurrent. However, private fusions may still be valuable as potential patient-specific biomarkers for diagnosis and treatment.