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. 2023 Jun 16;29(18):3706–3716. doi: 10.1158/1078-0432.CCR-23-0797

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.