Table 1. Distribution of PTCs by the pattern of DNA damage that generated the driver.
Alternative end-joining (alt-EJ), base pair (bp), DNA double-strand break (DNA DSB), nonhomologous end-joining (NHEJ), papillary thyroid carcinoma (PTC), single-strand annealing (SSA), structural variant (SV), The Cancer Genome Atlas (TCGA), and whole-genome sequencing (WGS).
| Chornobyl Tissue Bank* | TCGA (n = 69)† | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Driver type | Comments | Total (n = 355) | 131I-exposed (n = 285) | 131I-unexposed (n = 70) | |||||||
| Detailed classification | n | (%)‡ | n | (%)‡ | n | (%)‡ | n | (%)‡ | |||
| Fusion/SV driver | 140 | (100.0%) | 113 | (100.0%) | 27 | (100.0%) | 69 | (100.0%) | |||
| # Breaks | Gain/loss at the breakpoint | ||||||||||
| 2 | <20 bp at both breakpoints | DNA DSBs, enriched for repair by NHEJ or alt-EJ without delay in repair; no DNA fragment loss | 66 | (47.1%) | 63 | (55.8%) | 3 | (11.1%) | 17 | (24.6%) | |
| 2 | <1000 bp at both breakpoints (20–999 bp at ≥1 breakpoint) | DNA DSBs; unknown contribution of repair mechanisms (NHEJ, alt-EJ, SSA) with delay in repair and/or DNA fragment loss | 14 | (10.0%) | 11 | (9.7%) | 3 | (11.1%) | 13 | (18.8%) | |
| 2 | ≥1000 bp loss at ≥1 breakpoint | DNA DSBs; unknown contribution of repair mechanisms (NHEJ, alt-EJ, and SSA) and potential for long delay in repair and/or DNA fragment loss | 4 | (2.9%) | 3 | (2.7%) | 1 | (3.7%) | 3 | (4.3%) | |
| ≥3 | <20 bp at all breakpoints | DNA DSBs, enriched for repair by NHEJ or alt-EJ without delay in repair; no DNA fragment loss | 1 | (0.7%) | 1 | (0.9%) | 0 | 1 | (1.4%) | ||
| ≥3 | <1000 bp at all breakpoints (20–999 bp at ≥1 breakpoint) | DNA DSBs; unknown contribution of repair mechanisms (NHEJ, alt-EJ, and SSA) with delay in repair and/or DNA fragment loss | 7 | (5.0%) | 6 | (5.3%) | 1 | (3.7%) | 7 | (10.1%) | |
| ≥3 | ≥1000 bp loss at ≥1 breakpoint | DNA DSBs; unknown contribution of repair mechanisms (NHEJ, alt-EJ, SSA) and potential for long delay in repair and/or DNA fragment loss | 32 | (22.9%) | 20 | (17.7%) | 12 | (44.4%) | 24 | (34.8%) | |
| Other special categories | |||||||||||
| Large deletion (≥1000 bp) | DNA DSBs | 6 | (4.3%) | 3 | (2.7%) | 3 | (11.1%) | 1 | (1.4%) | ||
| Large duplication (≥1000 bp; not tandem) | DNA DSBs; microhomology-mediated break-induced replication | 3 | (2.1%) | 0 | 3 | (11.1%) | 1 | (1.4%) | |||
| Tandem duplication (≥1000 bp) | DNA DSBs | 1 | (0.7%) | 0 | 1 | (3.7%) | 2 | (2.9%) | |||
| Templated insertion | DNA DSBs; microhomology-mediated break-induced replication | 3 | (2.1%) | 3 | (2.7%) | 0 | 0 | ||||
| Dicentric | DNA DSBs; repaired chromosome resulted in two centromeres | 2 | (1.4%) | 2 | (1.8%) | 0 | 0 | ||||
| Chromothripsis | DNA DSBs | 1 | (0.7%) | 1 | (0.9%) | 0 | 0 | ||||
| Mutation driver | 215 | (100.0%) | 172 | (100.0%) | 43 | (100.0%) | |||||
| SBS | 200 | (93.0%) | 163 | (94.8%) | 37 | (86.0%) | |||||
| Dinucleotide substitution | 7 | (3.3%) | 5 | (2.9%) | 2 | (4.7%) | |||||
| Deletion | Potentially caused by DNA DSB repair | 1 | (0.5%) | 1 | (0.6%) | 0 | |||||
| Insertion | Potentially caused by DNA DSB repair | 1 | (0.5%) | 1 | (0.6%) | 0 | |||||
| Multiple mutations | 6 | (2.8%) | 2 | (1.8%) | 4 | (9.3%) | |||||
*Samples from the Chornobyl study eligible for this analysis were restricted to those with available WGS data, high tumor purity (>20%), and no evidence of tumor contamination in the normal tissue; we also excluded one tumor that did not have a known PTC driver, resulting in a total of 355 PTCs.
† Samples from the TCGA study eligible for this analysis were restricted to those with known fusion/SV drivers, available WGS data, and no known prior radiation exposure, resulting in a total of 69 PTCs.
‡ Column percent for fusion/SV and mutation drivers separately.