The mutational landscape of CLL. (A) The discovery of recurrently CLL mutated genes has become more sensitive with increased cohort size, with the estimated sensitivity calculated through saturation analysis^6,12,26 ; (B) Frequency of gene mutations depending on the course of the disease. “Early” (newly diagnosed and untreated patients); “Frontline” (untreated patients with symptomatic CLL requiring therapy); and “R/R” (relapsing or refractory patients). Unselected cohorts have been included from: DFCI/Broad Institute,¹²  Amedeo Avogadro University of Eastern Piedmont, Novara and Sapieza University (Rome, Italy)/Columbia University (New York)²⁷ ; ERIC ²⁸ ; MLL²⁹ ; and SCALE.³⁰  Reported are also series from clinical trials: UK LRF CLL4^31,32 ; GCLLSG CLL8,³³  CLL2H,³⁴  and CLL3X³⁵ ; GCFLLC/MW-GOELAMS ICLL01, and UK NCRN CLL201 and CLL202.³⁶  DCFI, Dana-Farber Cancer Institute; ERIC, European Research Initiative on CLL; GCFLLC/MW-GOELAMS, French CLL Intergroup; GCLLSG, German CLL Study Group; MLL, Munich Leukemia Laboratory; SCALE, Scandinavian Lymphoma Etiology; UK LRF, United Kingdom Lymphoma Research Foundation; UK NCRN, United Kingdom National Cancer Research Network.