Transcriptome Sequencing to Detect Gene Fusions in Cancer

Transcriptome Sequencing to Detect Gene Fusions in Cancer

2009 March 5 | Christopher A. Maher1,3, Chandan Kumar-Sinha1,3,†, Xuhong Cao1,2, Shanker Kalyana-Sundaram1,3, Bo Han1,3, Xiaojun Jing1,3, Lee Sam1,3, Terrence Barrette1,3, Nallasivam Palanisamy1,3, and Arul M. Chinnaiyan1,2,3,4,5,‡
A study published in *Nature* (2009) describes the use of transcriptome sequencing to detect gene fusions in cancer. Researchers used integrative analysis of long and short read transcriptome sequencing to identify novel gene fusions. They successfully re-discovered the BCR-ABL1 fusion in chronic myelogenous leukemia and the TMPRSS2-ERG fusion in prostate cancer. The study also identified several new gene fusions in cancer cell lines and tumors, including USP10-ZDHHC7, HJURP-EIF4E2, and INPP4A-HJURP. These fusions were validated experimentally and showed potential as diagnostic markers and therapeutic targets. The study highlights the importance of gene fusions in cancer, which are believed to be a major category of 'cancer genes'. Gene fusions can result in fusion proteins or drive the expression of oncogenes. The researchers developed an integrative approach combining long and short read sequencing to detect chimeric transcripts. This method allowed them to identify and validate gene fusions that were previously undetectable. The study also identified read-through events, which are chimeric transcripts between neighboring genes. These events were more broadly expressed across both malignant and benign samples compared to gene fusions, which were specific to cancer cells. The researchers extended their methodology to tumor samples and identified additional gene fusions, including SLC45A3-ELK4, which was found to be recurrent in prostate cancer and not associated with detectable DNA aberrations. The study emphasizes the importance of identifying and characterizing gene fusions in cancer. It suggests that these fusions may play a causal role in carcinogenesis and could be important therapeutic targets. The researchers also developed a classification system for chimeric transcripts, distinguishing between inter-chromosomal and intra-chromosomal fusions, as well as read-through events. The study demonstrates the power of transcriptome sequencing in detecting gene fusions and highlights the need for further research into their role in cancer.A study published in *Nature* (2009) describes the use of transcriptome sequencing to detect gene fusions in cancer. Researchers used integrative analysis of long and short read transcriptome sequencing to identify novel gene fusions. They successfully re-discovered the BCR-ABL1 fusion in chronic myelogenous leukemia and the TMPRSS2-ERG fusion in prostate cancer. The study also identified several new gene fusions in cancer cell lines and tumors, including USP10-ZDHHC7, HJURP-EIF4E2, and INPP4A-HJURP. These fusions were validated experimentally and showed potential as diagnostic markers and therapeutic targets. The study highlights the importance of gene fusions in cancer, which are believed to be a major category of 'cancer genes'. Gene fusions can result in fusion proteins or drive the expression of oncogenes. The researchers developed an integrative approach combining long and short read sequencing to detect chimeric transcripts. This method allowed them to identify and validate gene fusions that were previously undetectable. The study also identified read-through events, which are chimeric transcripts between neighboring genes. These events were more broadly expressed across both malignant and benign samples compared to gene fusions, which were specific to cancer cells. The researchers extended their methodology to tumor samples and identified additional gene fusions, including SLC45A3-ELK4, which was found to be recurrent in prostate cancer and not associated with detectable DNA aberrations. The study emphasizes the importance of identifying and characterizing gene fusions in cancer. It suggests that these fusions may play a causal role in carcinogenesis and could be important therapeutic targets. The researchers also developed a classification system for chimeric transcripts, distinguishing between inter-chromosomal and intra-chromosomal fusions, as well as read-through events. The study demonstrates the power of transcriptome sequencing in detecting gene fusions and highlights the need for further research into their role in cancer.
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