%0 Journal Article
%T Identification of gene fusion transcripts by transcriptome sequencing in BRCA1-mutated breast cancers and cell lines
%A Kevin CH Ha
%A Emilie Lalonde
%A Lili Li
%A Luca Cavallone
%A Rachael Natrajan
%A Maryou B Lambros
%A Costas Mitsopoulos
%A Jarle Hakas
%A Iwanka Kozarewa
%A Kerry Fenwick
%A Chris J Lord
%A Alan Ashworth
%A Anne Vincent-Salomon
%A Mark Basik
%A Jorge S Reis-Filho
%A Jacek Majewski
%A William D Foulkes
%J BMC Medical Genomics
%D 2011
%I BioMed Central
%R 10.1186/1755-8794-4-75
%X 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.Gene fusions are the result of aberrant chromosomal translocations that joins together the exons of two unrelated genes, producing a chimeric mRNA transcript and protein. Many gene fusions that contribute to oncogenesis
%U http://www.biomedcentral.com/1755-8794/4/75