Molecular analysis of telomere length in follicular lymphomas. Its participation in tumor progression]

Telomeres are essential for maintaining chromosomal integrity and stability. We studied here telomere length (TL) in bone marrow and/or lymph node from 36 patients: 29 with follicular lymphoma (FL) at diagnosis and 7 with diffuse large B cell lymphoma secondary to FL (S-DLBCL). TL was evaluated using terminal restriction fragments (TRF) assay. BCL-2 gene rearrangement was analyzed by nested and long distance PCR. Mean TRF values showed significant telomere shortening in FL (4.18 +/- 0.18 Kb) and S-DLBCL (3.31 +/- 0.25 Kb) respect to controls (8.50 +/- 0.50 Kb) (p < 0.001). Differences between both histological subtypes (p = 0.036) were also detected. Moreover, the samples positive for BCL-2 rearrangements showed longer TL (4.25 +/- 0.19 Kb) than the negative ones (3.39 +/- 0.30 Kb) (p = 0.023). A trend to telomere shortening was observed when Major Breakpoint Region (MBR-J(H)), minor cluster region (mcr-J(H)) and BCL-2 negative patients were compared (4.35 +/- 0.21 Kb; 3.84 +/- 0.45 Kb and 3.39 +/- 0.30 Kb, respectively). Our results show a TL reduction in FL and S-DLBCL, with significant short TRFs in the last group, suggesting the participation of telomere shortening in tumor progression. Furthermore, the differences detected between BCL-2 positive and negative FL support the involvement of diverse pathogenic mechanisms.