Mutations of the 5′ noncoding region of the BCL-6 gene in primary bone lymphomas

Somatic point mutations of the 5′ noncoding region of the BCL-6 gene have been described as genetic alterations in non-Hodgkin lymphomas (NHL). They are more frequent in diffuse large B cell (DLBCL) and follicular lymphomas (FL). This study aims to analyse the presence and distribution of BCL-6 gene mutations in a large series of primary bone lymphomas (PBL), a rare extranodal presentation of NHL frequently associated with diffuse large cell morphology. Fifty-three cases of PBL were examined. Mutations were detected with non-radioisotopic polymerase chain reaction-single strand conformation polymorphism and visualized with fluorescent cycle sequencing. Among stage I_E PBL, there were 30 cases of DLBCL and one each of follicular, anaplastic large cell and peripheral T-cell lymphoma. The stage II_E PBL included six DLBCL and one lymphoplasmacytic lymphoma, whereas within stage IV PBL there were 12 DLBCL and one Burkitt lymphoma. Fifteen patients (28%) displayed mutational events. In nine cases there were more than one BCL-6 mutation. Only DLBCL displayed mutations (31%). Mutations included single base-pair substitutions (16 transitions and ten transversions) and a single point insertion (ins A 427-28). The frequency of mutations resulted lower in DLBCL of the PBL category than in the majority of other extranodal large cell lymphomas. The prevalence of mutations was higher in stage I_E PBL than in more advanced stages of the disease (II_E + IV) (p=0.02). Our results reinforce the observation of heterogeneity of the DLBCL included in the clinical category of PBL.