Transcriptome Sequencing to Detect Gene Fusions in Cancer

By C. Maher, Chandan Kumar-Sinha, Xuhong Cao, Shanker Kalyana-Sundaram, B. Han, Xiaojun Jing, L. Sam, T. Barrette, N. Palanisamy, Arul M. Chinnaiyan. Nature, 2009

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Recurrent gene fusions, typically associated with haematological malignancies and rare bone and soft-tissue tumours, have recently been described in common solid tumours. Here we use an integrative analysis of high-throughput long- and short-read transcriptome sequencing of cancer cells to discover novel gene fusions. As a proof of concept, we successfully used integrative transcriptome sequencing to ‘re-discover’ the BCR–ABL1 (ref. 10) gene fusion in a chronic myelogenous leukaemia cell line and the TMPRSS2–ERG gene fusion in a prostate cancer cell line and tissues. Additionally, we nominated, and experimentally validated, novel gene fusions resulting in chimaeric transcripts in cancer cell lines and tumours. Taken together, this study establishes a robust pipeline for the discovery of novel gene chimaeras using high-throughput sequencing, opening up an important class of cancer-related mutations for comprehensive characterization.

Subfields: Cancer Research, Molecular Biology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/42f3486128a5e5be1db9a8fe9a124e43f602a5c8

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Citations in the corpus

deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data (2011, background): “The size selection step of the RNA-Seq library construction protocol results in a collection of cDNA fragments with lengths that we approximate with the inferred fragment length distribution P(L) derived from concordant alignments [16,17].”
Gene Mapping via Bulked Segregant RNA-Seq (BSR-Seq) (2012, background): “RNA-Seq reads can also be mined for DNA sequence polymorphisms such as single nucleotide polymorphisms (SNPs) [29,30], which can be converted into genetic markers [18,31–34].”
Real-time DNA sequencing from single polymerase molecules. (2010, methodology): “…have changed whole-genome sequencing projects into routine procedures (reviewed in Mardis, 2008) and have been adapted to other areas, such as transcriptome sequencing and epigenetics (Cloonan et al., 2008; Cokus et al., 2008; Fullwood et al., 2009; Maher et al., 2009; Yassour et al., 2009).”
TopHat-Fusion: an algorithm for discovery of novel fusion transcripts (2011, background): “‘Fusion’ genes formed by the breakage and re-joining of two different chromosomes have repeatedly been implicated in the development of cancer, notably the BCR/ABL1 gene fusion in chronic myeloid leukemia [7-9].”
Real-Time DNA Sequencing from Single Polymerase Molecules (2009, methodology): “Next-generation DNA sequencing methods have changed whole-genome sequencing projects into routine procedures (reviewed in Mardis, 2008) and have been adapted to other areas, such as transcriptome sequencing and epigenetics (Cloonan et al., 2008; Cokus et al., 2008; Fullwood et al., 2009; Maher et al”
Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study (2011, methodology): “We have adapted and refined our approach to achieve accurate gene fusion discovery from RNA-Seq data(25,26).”
A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis (2013, neutral): “fusion detection [10] or strand-specific expression”