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Prognostic significance of secondary cytogenetic alterations in follicular lymphomas

✍ Scribed by Nathalie A. Johnson; Abdul Al-Tourah; Carolyn. J. Brown; Joseph M. Connors; Randy D. Gascoyne; Douglas E. Horsman


Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
130 KB
Volume
47
Category
Article
ISSN
1045-2257

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✦ Synopsis


Abstract

Follicular lymphoma (FL) is an indolent lymphoma with a long median survival. Transformation to a more aggressive histology (TLy) is a major cause of mortality. The critical events leading to TLy are unknown. We assessed the prognostic significance of secondary cytogenetic alterations on overall survival (OS) and transformation from 210 diagnostic FL biopsies. We analyzed serial and transformed karyotypes for recurrent alterations that predict transformation. Over 10 years, 31% of cases developed TLy. The only alteration in diagnostic karyotypes that correlated with an inferior OS was an additional X chromosome in males only (P = 0.005) suggesting that other mechanisms including epigenetic factors and over‐expression of genes on the X chromosome may play a role in FL pathogenesis. In transformed karyotypes, 8q24 (MYC) translocations were common (14/37) and resulted in a median survival of 3 months posttransformation (P = 0.01). In serially obtained biopsies (28 pts), 43% of the later biopsies lacked the cytogenetic alterations found in the original FL karyotype, suggesting that karyotypic progression of FL is not strictly linear in all cases. Consequently, studying clonal evolution in FL using serial biopsies may not represent the full complexity of genetic alterations leading to transformation. Β© 2008 Wiley‐Liss, Inc.


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## Abstract Follicular lymphoma (FL) is characterized by the activation of __BCL2__ through t(14;18)(q32;q21). Additional acquired mutations are necessary to generate a fully malignant clonal proliferation. Many of these secondary genetic alterations are visible in the clonal karyotype; however, th