Most large structural variants in cancer genomes can be detected without long reads Journal Article
| Authors: | Choo, Z. N.; Behr, J. M.; Deshpande, A.; Hadi, K.; Yao, X.; Tian, H.; Takai, K.; Zakusilo, G.; Rosiene, J.; Da Cruz Paula, A.; Weigelt, B.; Setton, J.; Riaz, N.; Powell, S. N.; Busam, K.; Shoushtari, A. N.; Ariyan, C.; Reis-Filho, J.; de Lange, T.; Imieliński, M. |
| Article Title: | Most large structural variants in cancer genomes can be detected without long reads |
| Abstract: | Short-read sequencing is the workhorse of cancer genomics yet is thought to miss many structural variants (SVs), particularly large chromosomal alterations. To characterize missing SVs in short-read whole genomes, we analyzed ‘loose ends’—local violations of mass balance between adjacent DNA segments. In the landscape of loose ends across 1,330 high-purity cancer whole genomes, most large (>10-kb) clonal SVs were fully resolved by short reads in the 87% of the human genome where copy number could be reliably measured. Some loose ends represent neotelomeres, which we propose as a hallmark of the alternative lengthening of telomeres phenotype. These pan-cancer findings were confirmed by long-molecule profiles of 38 breast cancer and melanoma cases. Our results indicate that aberrant homologous recombination is unlikely to drive the majority of large cancer SVs. Furthermore, analysis of mass balance in short-read whole genome data provides a surprisingly complete picture of cancer chromosomal structure. © 2023, The Author(s). |
| Keywords: | somatic mutation; genetics; validation process; analysis; chromosome structure; phenotype; telomere; homologous recombination; melanoma; breast cancer; genetic variation; breast neoplasms; chromosome aberration; dna; algorithm; human genome; breast tumor; amplicon; genomics; genome; chromosome aberrations; gene dosage; genome, human; sequence analysis, dna; germline mutation; procedures; virus dna cell dna interaction; high throughput sequencing; high-throughput nucleotide sequencing; genomic structural variation; dna sequencing; humans; human; female; article; oncogenomics; junction balance analysis; non allelic homologous recombination |
| Journal Title: | Nature Genetics |
| Volume: | 55 |
| Issue: | 12 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-12-01 |
| Start Page: | 2139 |
| End Page: | 2148 |
| Language: | English |
| DOI: | 10.1038/s41588-023-01540-6 |
| PUBMED: | 37945902 |
| PROVIDER: | scopus |
| PMCID: | PMC10703688 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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154Ariyan -
688Busam -
93Setton -
244Shoushtari -
632Weigelt -
639Reis-Filho -
145Da Cruz Paula
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