Loss of COPS7B and COPS8 genes on chromosome 2q37 increases in incidence at LEN and LEN-then-POM refractory states. (A) Genes (n = 23) and their chromosome location, identified from ≥2 published pharmacogenetic screens (n = 5 screens; supplemental Tables 1 and 2). (B) Incidence of mutation or deletion (excluding cases with copy neutral LOH) in the 23 genes listed in (A) in 3 patient datasets: NDMM, LEN-refractory, and POM-refractory. Incidence of 1q21 gain/amp (CKS1B), 1p loss (CDKN2C), and 17p loss (TP53) across the 3 patient datasets are provided for context. (C) Proportion of samples with COPS7B and COPS8 copy loss (excluding cases with copy neutral LOH) (LH y-axis) and their CCFs (RH y-axis) at NDMM, LEN-, and POM-refractory states. Significance detected by χ2 test for trend in proportions with false discovery rate correction (when compared with all 23 genes; for other genes see supplemental Figure 2). Note: no instances of homozygous COPS7B or COPS8 loss were identified. Arrow in (C)ii marks a narrow point in CCF distribution taken as cutoff to divide high CCF (>0.75) from low CCF (<0.75) cases (used in supplemental Figure 5). (D) Difference in COPS7B and COPS8 gene expression (mRNA expression by TPM) with presence or absence of gene copy loss. Significance detected by unpaired 2-sided t test. Abbreviations: LOH, loss of heterozygosity; NDMM, newly diagnosed multiple myeloma; TPM, transcripts per million reads mapped.
