Nallasivam Palanisamy

The research goals of my laboratory are discovering and characterizing gene fusions in cancer and understanding their role in carcinogenesis from a translational research perspective. Genomic technologies include high-density array comparative genomic hybridization, advanced molecular cytogenetic technologies including FISH, spectral karyotyping, gene expression microarrays, next-generation sequencing, and spatial transcriptomics technologies are employed as high throughput methodologies to investigate the transcriptional and genomic architectures of the solid cancer genome. Our group pioneered the application of next-generation sequencing technology to discover new recurrent gene fusions in cancer. The primary goal of this approach is to identify novel gene fusions specific to each cancer type. Employing the next-generation sequencing approach emphasizing RNAseq provided a unique opportunity to interrogate the cancer transcriptome unbiasedly to identify novel gene fusions, alternative transcripts, non-coding RNA, SNP’s, micro-RNA, and pseudogenes not detectable by gene expression microarray analysis. We recently discovered a new recurrent gene fusion in a subset of ETS-negative prostate cancer. Long-term goals are to conduct advanced research applying next-generation sequencing technology for an integrated analysis using RNA and DNA processing data, genotyping, chip sequence, gene expression, copy number analysis for variations and rearrangements, and methylation analysis to comprehensively understand the cancer genome's genetic complexity. This work will lead to identifying novel biomarkers for routine diagnosis and treatment follow-up. 

Our group has pioneered the application of next-generation sequencing technology for transcriptome sequencing and developed methods for detecting gene fusions. Recurrent gene fusions involving ETS family genes in more than half of prostate cancer patients are made possible by a novel bioinformatics analytical approach. However, the ETS family genes are challenging to target with small molecule inhibitors due to the lack of enzymatic activity and the requirement of interaction with proteins to reach specificity. While screening the ETS-negative prostate cancers by transcriptome sequencing, we discovered novel recurrent druggable RAF kinase pathway gene fusions. Comprehensive analysis of other solid cancer revealed the RAF gene rearrangements in gastric and melanoma. These RAF gene fusions are targetable with BRAF and MEK inhibitors. This finding is a significant advancement in identifying and treating subsets of the patient population with RAF family gene rearrangement.