Title | Most large structural variants in cancer genomes can be detected without long reads. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Choo Z-N, Behr JM, Deshpande A, Hadi K, Yao X, Tian H, Takai K, Zakusilo G, Rosiene J, Paula ADa Cruz, Weigelt B, Setton J, Riaz N, Powell SN, Busam K, Shoushtari AN, Ariyan C, Reis-Filho J, de Lange T, ImieliĆski M |
Journal | Nat Genet |
Volume | 55 |
Issue | 12 |
Pagination | 2139-2148 |
Date Published | 2023 Dec |
ISSN | 1546-1718 |
Keywords | Breast Neoplasms, Chromosome Aberrations, Female, Genome, Human, Genomic Structural Variation, Genomics, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, DNA |
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. |
DOI | 10.1038/s41588-023-01540-6 |
Alternate Journal | Nat Genet |
PubMed ID | 37945902 |
PubMed Central ID | PMC10703688 |
Grant List | R35 CA210036 / CA / NCI NIH HHS / United States F31 CA232465 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States F30 CA268747 / CA / NCI NIH HHS / United States |
Submitted by bel2021 on February 16, 2024 - 10:43am