Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma: prognostic significance of E2F-1 and p16INK4A.

摘要: In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based registry for alterations of RB1 pathway at genetic (RB1 and CDK4) protein (pRb, cyclin D1, D3, CDK4, E2F-1) level. The results were correlated with data our previous studies CDKN2A deletion hypermethylation, other p53 components, p27Kip1 expression, proliferation, as well clinical outcome, including prognosis. We found aberrant pRb expression in four (12%) DLCLs. One these had point mutation intron 3 10 bp downstream exon generating novel splice signal. Seven tumours (21%) showed D3 overexpression, all three thyroid lymphomas (P = 0.006). Cyclin overexpression p16INK4A/pRb aberrations mutually exclusive, supporting an oncogenic role DLCL. p16INK4A inactivation, or was identified 18 DLCLs (53%). Combining that 82% pathways, both pathways altered 13 cases (38%). Low E2F-1 associated treatment failure 0.020), multivariate analysis overall survival low (relative risk 6.9; P 0.0037) inactivation 3.3; 0.0247) independent prognostic markers. These support tumour suppressor gene strongly suggest are important development Furthermore, may serve markers patients this type lymphoma.