‘ ‘ focus on . . . ’ ’ session : lymphoma biology 127 DETECTION OF MYC MUTATIONS IN MOLECULARLY

Results: 91/267 cases (34%) displayed MYC PR mutations. The mutation frequency (MF) was significantly higher in molecular BL (mBL) identified by GE than in nonmolecular BL (non-mBL) (0,63% vs. 0,18%, p<0,0001). Interestingly 27 non-mBL lacking MYC translocations carried MYC PR mutations indicating aberrant somatic hypermutation. MYC TAD mutations were present in 62/267 cases (23%) including 36/ 64 mBL. TAD mutations were strongly associated with MYC-IGH fusions (p<0,0001) but also occured in 8 MYC-negative cases. In 17 cases, TAD mutations involved known phosphorylation sites at MYC box I (Pro 57, Thr58, Pro59, Pro60, Ser64) and in 13 cases MYC box II including a novel mutational hotspot at Phe138. MYC MF did not correlate with IGH MF, genetic complexity and gene expression of MYCor MYC target genes. However, mBL with MYC PR mutations had an unfavourable prognosis in comparison with unmutated mBL.