Jethwa, Alexander2; Hüllein, Jennifer2; Stolz, Tatjana2; Blume, Carolin2; Sellner, Leopold2; Jauch, Anna2; Sill, Martin2; Kater, Arnon P2; te Raa, G Doreen2; Geisler, Christian3; van Oers, Marinus2; Dietrich, Sascha2; Dreger, Peter2; Ho, Anthony D2; Paruzynski, Anna2; Schmidt, Manfred2; von Kalle, Christof2; Glimm, Hanno2; Zenz, Thorsten2
1 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently mutated (16.3%, 16.9%, 10.7%). We found evidence for subclonal mutations in 67.5% of CLL cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in CLL. Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in CLL.
British Journal of Haematology, 2013, Vol 163, Issue 4, p. 496-500