Fig. 4

BRCA1/2 signature as a potential therapeutic target for ESCC. a Top bar represents the contribution of signature 3 in each ESCC. Colored squares indicate dominant mutational signature and LOH status of BRCA1/2. Deleterious germline and somatic mutations in the HR pathway are shown at the bottom of the heat map. b, c Comparison of signature 3 activity in ESCCs with or without BRCA1/2 mutation in 39-Mseq cohort (b) and additional 508-WGS cohort (c). d Knockdown of BRCA1 and BRCA2 significantly increased sensitivity of KYSE410 cells to cisplatin. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, n.d. means not detected. Error bars are defined as s.d. Source data are provided as a Source Data file. e Receiver operating characteristic (ROC) curves for alterations in BRCA1/2 germline mutation predicted based on signature 3 levels in 39-Mseq cohort (left) and additional 508-WGS cohort (right)