Age-Related Chromosomal Aberrations in Patients with Diffuse Large B-Cell Lymphoma

Background: In diffuse large B-cell lymphoma (DLBCL), where the mean age of diagnosis is 70, it has been demonstrated that certain chromosomal and genetic aberrations are known to increase with advancing age. Additionally, younger patients (pts) with DLBCL have aberrations associated with a better prognosis. Our study aims to determine if there are other genetic aberrations associated with DLBCL based on age.

Methods: The National Cancer Institute's Mitelman Database of Chromosome Aberrations and Gene Fusions was used to identify pts with DLBCL. Pts with DLBCL chromosomal aberration analysis results were divided into 4 groups based on age (0-30, 31-50, 51-70, >71) and examined by chi square analysis for trend. Mantel-Cox log-rank test was used for survival analysis. All p-values were two sided and a value of less than 0.05 was used for significance.

Results: 1004 DLBCL pts were identified, 541 men and 459 women (1.179 male to female) with a median age (ma) of 61. These pts were divided into four categories: <30 (102), 31-50 (171), 51-70 (488), >71(242). 7 aberrations were found to have significant age-related differences within this population: Trisomy 19p13 (ma 72, p=0.0021), polysomy 18 (ma 66, p=0.0418), t8;14 (ma 54, p=0.0003), t11;14 (ma 69.5, p=0.0185), t2;3(ma 50.5, p=0.001), t2;5(ma 10.5 p=0.0001), and t14;18(ma 65, p=0.0003). Each translocation localized to a specific age category, most in middle age. t2;5 translocations were exclusively increased in pts under 18. Survival differences were non-significant (p=0.1459) between these aberrations, with an average overall survival of 14 months. 19p13 addition had the shortest median survival (7 months), while the t(2;3) translocation was associated with the longest survival (20 months).

Conclusions: Genetic aberrations in DLBCL were associated with significant age-related accumulations. This suggests that pts who develop DLBCL are more likely to accumulate different translocations depending on their age at the time of DLBCL development.