BRCA2 promoter hypermethylation as a biomarker for the leukemic transformation of myeloproliferative neoplasms

Supplementary table 1. Probes flanking the promoter region of 236 DDR genes retained for differential methylation analysis

Supplementary table 2. MPN and methylation analysis

Supplementary Figure 1 Differential methylation analysis revealed HR gene promoter methylation in MPNs-LT

A) Flow chat illustrating the pipeline of differential methylation analysis in 241 DDR genes.

B) Bisulfite treatment and qPCR quantification of RAD50, POLD1, TOP3B and FEN1 promoter methylation in an in-house cohort of 5 MPNs-LT, 75 cMPNs, and 50 healthy donors (two-sample t-test, ***P < 0.001, ****P < 0.0001, n.s. not significant).

Supplementary Figure 2 Single base substitution mutational signature in cMPNs and MPNs-LT

A) Comparison of mutational signature 1 (aging), 5 (transcriptional strand T>C substitutions), 6 (mismatch repair deficiency), 12 (unknown aetiology), 20 (mismatch repair deficiency), and 21 (unknown aetiology) between cMPNs and MPNs-LT. (two-sample t-test, *P < 0.05, n.s. not significant).

B) Correlation between mutational signature 5 and signature 3 in the in-house MPNs cohort.