Unscrambling cancer genomes via integrated analysis of structural variation and copy number
- Author(s)
- Shale, C; Cameron, DL; Baber, J; Wong, M; Cowley, MJ; Papenfuss, AT; Cuppen, E; Priestley, P;
- Details
- Publication Year 2022-04-13,Volume 2,Issue #4,Page 100112
- Journal Title
- Cell Genomics
- Abstract
- Complex somatic genomic rearrangements and copy number alterations are hallmarks of nearly all cancers. We have developed an algorithm, LINX, to aid interpretation of structural variant and copy number data derived from short-read, whole-genome sequencing. LINX classifies raw structural variant calls into distinct events and predicts their effect on the local structure of the derivative chromosome and the functional impact on affected genes. Visualizations facilitate further investigation of complex rearrangements. LINX allows insights into a diverse range of structural variation events and can reliably detect pathogenic rearrangements, including gene fusions, immunoglobulin enhancer rearrangements, intragenic deletions, and duplications. Uniquely, LINX also predicts chained fusions that we demonstrate account for 13% of clinically relevant oncogenic fusions. LINX also reports a class of inactivation events that we term homozygous disruptions that may be a driver mutation in up to 9% of tumors and may frequently affect PTEN, TP53, and RB1.
- Publisher
- Elsevier
- Keywords
- Linx; cancer genomics; ecDNA; gene fusion; genomic rearrangement; genomic shard; homozygous disruption; mobile element insertion; reciprocal duplication; structural variation
- Research Division(s)
- Bioinformatics
- PubMed ID
- 36776527
- Publisher's Version
- https://doi.org/10.1016/j.xgen.2022.100112
- Open Access at Publisher's Site
https://doi.org/10.1016/j.xgen.2022.100112 - Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-02-16 04:00:29
Last Modified: 2023-02-17 11:13:43