Abstract:
BACKGROUND:Immunoglobulin gene somatic hypermutation is a biologically relevant and clinically useful prognostic factor in different types of low-grade B-cell lymphomas, including chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. DESIGN AND METHODS:With the aim of identifying surrogate markers of somatic hypermutation, a combined investigation of IgV(H) mutational status and expression profiles of 93 samples from patients with small B-cell lymphoma was performed. RESULTS:The analysis identified an somatic hypermutation signature of genes involved in the regulation of gene transcription, DNA repair and replication, and chromosome maintenance. Eight of these genes were subjected to protein analysis using tissue microarrays, for a set of 118 cases. We found a clear link between RAD51C and CDK7 protein expression and somatic hypermutation status, in that positive expression of either marker was significantly associated with a mutated status (p<0.003). We also found that positive expression of TFDP1 and POLA was significantly associated with ongoing somatic hypermutation (p<0.001). To assess the potential clinical applicability of these somatic hypermutation markers, we studied a series of cases of mantle cell lymphoma included in a tissue microarray. The expression of RCC1 and CDK7, separately and together, was found to be significantly associated with longer overall survival. CONCLUSIONS:An somatic hypermutation signature has been identified for different types of small B-cell lymphoma. This has a potential mechanistic and diagnostic value.
journal_name
Haematologicajournal_title
Haematologicaauthors
Tracey L,Aggarwal M,García-Cosio M,Villuendas R,Algara P,Sánchez-Beato M,Sánchez-Aguilera A,García JF,Rodríguez A,Camacho FI,Martínez N,Ruiz-Ballesteros E,Mollejo M,Piris MAdoi
10.3324/haematol.12999subject
Has Abstractpub_date
2008-08-01 00:00:00pages
1186-94issue
8eissn
0390-6078issn
1592-8721pii
haematol.12999journal_volume
93pub_type
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