RNA-Seq Analysis to Detect Abnormal Fusion Transcripts Linked to Chromothripsis

Abstract

RNA-Seq approach enables the detection and characterization of fusion or chimeric transcript associated to complex genome rearrangement. Until now, these events are classically identified at DNA level.Here we describe a complete procedure including a novel way of analyzing reads that combines genomic locations and local coverage to directly infer chimeric junctions with a high sensitivity and specificity, allowing identification of different classes of chimeric RNA events. We also recommend the best practices for the bioinformatics analysis and describe the experimental process for RNA validation using real-time PCR and sequencing.

Understanding Intratumor Heterogeneity and Evolution in NSCLC and Potential New Therapeutic Approach

“…These large-scale genomic rearrangements are usually related to the aggressive character of cancer [ 28 ]; however, cancers with an extreme level of chromosomal instability tend to exhibit more favorable prognosis, as compared with intermediate levels [ 42 , 43 , 44 ]. In addition, oncogenic fusion genes caused by chromothripsis may function as driver mutations and thus represent promising therapeutic targets [ 40 , 45 , 46 , 47 ].…”