Genomic translocations frequently lead to the generation of gene fusions with oncogenic properties. RNA sequencing has allowed gene expression profiling and detection of previously unknown, alternatively spliced and gene fusion transcripts with potential oncogenic role.
Detecting Gene Fusions with RNA Sequencing
Whole-genome DNA sequencing studies have identified numerous chromosomal translocations that potentially result in gene fusions; however, it is uncertain how many of the fusion genes are actually expressed. Alternatively, RNA-sequencing provides a more efficient approach to directly identify transcripts generated by gene fusions that could be translated into tumorigenic chimeric proteins1.
The biogenesis, development and metastases of cancer are associated with many variations in the transcriptome. Alternative splicing of genes is a major post-transcriptional regulation mechanism that is involved in many types of cancer. The next-generation sequencing applied on RNAs (RNA-Seq) provides a new technology for studying transcriptomes. It provides an unprecedented opportunity for quantitatively studying alternative splicing in a systematic way2.
Recurrent gene rearrangements play significant roles in subsets of carcinomas and suggest that transcriptome sequencing may serve to identify patients with rare, actionable gene fusions. The identification of gene-fusions may be important for the development of personalized therapies for a subgroup of breast cancer patients3.
- Verigos J, Magklara A (2015) Revealing the Complexity of Breast Cancer by Next Generation Sequencing. Cancers (Basel) 7(4):2183-200.
- Feng H, Qin Z, Zhang X. (2013) Opportunities and methods for studying alternative splicing in cancer with RNA-Seq. Cancer Lett 340(2):179-91.
- Robinson DR, Kalyana-Sundaram S, Wu YM, Shankar S, Cao X, Ateeq B, Asangani IA, Iyer M, Maher CA, Grasso CS, Lonigro RJ, Quist M, Siddiqui J, Mehra R, Jing X, Giordano TJ, Sabel MS, Kleer CG, Palanisamy N, Natrajan R, Lambros MB, Reis-Filho JS, Kumar-Sinha C, Chinnaiyan AM. (2011) Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancer. Nat Med 17(12):1646-51.