Figure 1. Identification of a relapse-specific C481S BTK mutation in MCL by longitudinal integrative WES and WTS.
A, schema for the C481S mutation in BTK and WES analysis of single nucleotide variations (SNVs; % of alternative allele) in the DNA of cheek swab (CS) and MCL cells from serial biopsies of Pt 1. The accession number for the protein sequence is NP_000052.1. B, integrative genomics viewer (IGV) visualization of nucleotide substitution and alignments of BTK on chromosome X (ChrX):100611161-100611166. C, identification by Sanger sequencing of G1442C and C1443T in BTK in bone marrow and spleen biopsies at relapse (r_IbBM, r_IbSP), and the wild type sequence in the bone marrow biopsy immediately before initiation of ibrutinib treatment (p_Ib3). D and E, WTS analysis of mRNA abundance (RPKM, reads per kilobase per million reads; bars) and non-synonymous SNVs (% of alternative allele, red line) in CDS and untranslated regions of genes commonly mutated in MCL. PBC: CD19+ B cells isolated from peripheral blood of healthy donors.