Unscrambling cancer genomes via integrated analysis of structural variation and copy number
Summary: 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 var...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-04-01
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| Series: | Cell Genomics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666979X22000325 |
| _version_ | 1828844100941512704 |
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| author | Charles Shale Daniel L. Cameron Jonathan Baber Marie Wong Mark J. Cowley Anthony T. Papenfuss Edwin Cuppen Peter Priestley |
| author_facet | Charles Shale Daniel L. Cameron Jonathan Baber Marie Wong Mark J. Cowley Anthony T. Papenfuss Edwin Cuppen Peter Priestley |
| author_sort | Charles Shale |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-12T20:59:34Z |
| format | Article |
| id | doaj.art-070cdb7599c142749c125eef2ee342db |
| institution | Directory Open Access Journal |
| issn | 2666-979X |
| language | English |
| last_indexed | 2024-12-12T20:59:34Z |
| publishDate | 2022-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Genomics |
| spelling | doaj.art-070cdb7599c142749c125eef2ee342db2022-12-22T00:12:12ZengElsevierCell Genomics2666-979X2022-04-0124100112Unscrambling cancer genomes via integrated analysis of structural variation and copy numberCharles Shale0Daniel L. Cameron1Jonathan Baber2Marie Wong3Mark J. Cowley4Anthony T. Papenfuss5Edwin Cuppen6Peter Priestley7Hartwig Medical Foundation Australia, Sydney, NSW, Australia; Hartwig Medical Foundation, Science Park 408, Amsterdam, the NetherlandsHartwig Medical Foundation Australia, Sydney, NSW, Australia; Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, AustraliaHartwig Medical Foundation Australia, Sydney, NSW, Australia; Hartwig Medical Foundation, Science Park 408, Amsterdam, the NetherlandsChildren’s Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, NSW, Australia; School of Women’s and Children’s Health, UNSW Sydney, Kensington, NSW, AustraliaChildren’s Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, NSW, Australia; School of Women’s and Children’s Health, UNSW Sydney, Kensington, NSW, AustraliaBioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia; Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, AustraliaHartwig Medical Foundation, Science Park 408, Amsterdam, the Netherlands; Center for Molecular Medicine and Oncode Institute, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, the NetherlandsHartwig Medical Foundation Australia, Sydney, NSW, Australia; Hartwig Medical Foundation, Science Park 408, Amsterdam, the Netherlands; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666979X22000325cancer genomicsstructural variationgenomic rearrangementLINXhomozygous disruptiongene fusion |
| spellingShingle | Charles Shale Daniel L. Cameron Jonathan Baber Marie Wong Mark J. Cowley Anthony T. Papenfuss Edwin Cuppen Peter Priestley Unscrambling cancer genomes via integrated analysis of structural variation and copy number Cell Genomics cancer genomics structural variation genomic rearrangement LINX homozygous disruption gene fusion |
| title | Unscrambling cancer genomes via integrated analysis of structural variation and copy number |
| title_full | Unscrambling cancer genomes via integrated analysis of structural variation and copy number |
| title_fullStr | Unscrambling cancer genomes via integrated analysis of structural variation and copy number |
| title_full_unstemmed | Unscrambling cancer genomes via integrated analysis of structural variation and copy number |
| title_short | Unscrambling cancer genomes via integrated analysis of structural variation and copy number |
| title_sort | unscrambling cancer genomes via integrated analysis of structural variation and copy number |
| topic | cancer genomics structural variation genomic rearrangement LINX homozygous disruption gene fusion |
| url | http://www.sciencedirect.com/science/article/pii/S2666979X22000325 |
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