Paper - Review

DOI: 10.1038/s41586-019-1913-9

Abstract

A key mutational process ← in cancer
→ is structural variation
← which 1⃣ rearrangements delete 2⃣ amplify 3⃣ reorder genomic segments
→ range in size → from K-base to whole chromosome

Develop methods
→ to 1⃣ group 2⃣ classify 3⃣ describe somatic structural variants
← using 1⃣ PCAWG 2⃣ TCGA
← which aggregated whole-genome sequencing data
← from 2658 cancers ← across 38 tumor types

∴ 16 signatures of structural variation emerged

Deletions
→ have a multi-modal size distribution
→ assort unevenly ← across 1⃣ tumor types 2⃣ patients
→ are enriched ← in late-replicating regions
→ correlated ← with inversions

Tandem duplications
→ have a multi-modal size distribution
→ are enriched ← in early-replicating regions
→ are unbalanced translocations

Replication-based mechanisms ← of re-arrangement generate
→ varied chromosomal structures
← with low-level copy-number gains & frequent inverted re-arrangement

One prominent structure
← consists of 2-7 templates
→ copied ← from distinct regions of the genome
← strung together ← within one locus

❗: such cycles of template insertions
→ correlated ← with tandem duplications ← in liver cancer
→ frequently activate the telomerase gene → TERT

A wide variety of re-arrangement processes
→ are active in cancer
← generate complex configurations of the genome
← upon which selection can act

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