Molecular features of primary mediastinal B-cell lymphoma: involvement of p16(INK4A), p53 and c-myc

Primary mediastinal B-cell lymphoma (PMBL) shows chromosome 9p anomalies in 50% of cases. Based on reports that p16(INK4A) gene, located on this chrom osomal arm, is frequently altered in aggressive lymphomas, we analysed for alterations of this gene in 27 cases of PMBL, which were part of a series o f 32 PMBL cases that have been characterized for alterations in c-myc, p53, N-ras, bcl-1, bcl-2, bcl-6 and for Epstein-Barr virus (EBV) infection. Fou r cases showed p16(INK4A) gene anomalies, including three with promoter met hylation and one homozygous deletion. Eight PMBLs showed c-myc rearrangemen ts, Three additional cases showed sequence variations in the c-myc P2 promo ter, two of which consisted of the same germline variation involving a nove l polymorphic XhoI site. Pour tumours contained p53 gene mutations and thre e had clonal EBV infection. One case had a bcl-6 rearrangement. In conclusi on, our study shows that p16(INK4), c-myc and p53 alterations occur in 15%, 25% and 13% of PMBLs, respectively. EBV monoclonality was found in 9% of c ases, whereas no abnormality was detected in bcl-1, bcl-2 and N-ras. Thus, none of the common genetic aberrations seen in other types of non-Hodgkin's lymphomas appears to be stringently involved in the pathogenesis of this u nique lymphoma type.