Association between telomere length and BCL2 gene rearrangements in low- and high-grade non-Hodgkin lymphomas.
Telomere length based on terminal restriction fragment (TRF) assay was evaluated in cells of bone marrow, lymph node, or both from 53 non-Hodgkin lymphoma (NHL) patients: 44 with follicular lymphoma (FL) and 9 with secondary diffuse large B-cell lymphoma (S-DLBCL) to FL. The TRF data were correlated with BCL2 gene rearrangement evaluated by nested and long-distance polymerase chain reaction approaches. Peripheral blood cells from 12 healthy donors were studied as controls. Both groups of NHL patients revealed significant telomere shortening compared with controls (8.50 +/- 0.50 kb; P < 0.001), with significantly shorter TRFs in S-DLBCL (3.49 +/- 0.26 kb) than in FL cases (4.09 +/- 0.12 kb; P = 0.047). Patients carrying BCL2 gene rearrangements showed longer telomere length (4.19 +/- 0.14 kb) than those without (3.51 +/- 0.14 kb; P = 0.05). Among patients with FL, telomere length was shortest in patients without t(14;18), intermediate when breakpoints occurred in the minor breakpoint cluster region (3.97 +/- 0.33 kb), and greater when breakpoints occurred in the major breakpoint region (MBR) (4.24 +/- 0.15 kb), with significant differences between MBR and BCL2-negative cases (P = 0.033). Our findings support the existence of alternative genetic pathways involved in the origin of these FL subsets. Even though the number of S-DLBCL cases was small, they showed the shortest telomere length, suggesting that this parameter reflects another genetic alteration involved in the progression from FL to a higher-grade lymphoma.
Haydeé Cottliar
Alejandra Silvina
AS
Department of Genetics, Institute for Hematological Research, National Academy of Medicine, Instituto de Investigaciones Hematológicas Mariano R Castex, Academia Nacional de Medicina, Pacheco de Melo 3081, Buenos Aires, Argentina.
Noriega
María Fernanda
MF
Narbaitz
Marina
M
Rodríguez
Andrea
A
Slavutsky
Irma Rosa
IR
D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016615:Telomere / Q000235:genetics*
D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2; D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases; C040158:GTAC-specific type II deoxyribonucleases