Table 1.
Reversions as a mechanism of PARPi resistance detectable in cfDNA.
| Sample (WES) | Gene | Initial mutation | Reversion mutation (VAF in exome) | Findings in cfDNA |
|---|---|---|---|---|
| EVO-009–001-Bx | BRCA1 | Somatic p.L631Qfs*4a | c.1509_2366del; p.S425_C712fs | Confirmed in cfDNA (baseline and end of treatment) |
| EVO-009–006-Bx | BRCA2 | Germline c.7480C>T | c.7480C>A (20% A allele) | Confirmed in cfDNA (baseline, on-trial and time of progression) |
| EVO-009–013-Bx | BRCA1 | Germline c.2999del | c.3008_3009del (31.0%) | Confirmed in cfDNA (baseline only); amost somatic callers discard this as too many clustered events on short reads |
Note: Somatic reversions previously detected in post-PARPi progressed tumor tissue using WES. Of these, three were successfully detected, and two had no evidence in cfDNA.
aReversion detected but did not pass thresholds for high-confidence somatic mutation classification.