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.