Abstract

Genomic Analysis of Follicular Lymphoma Subgroups

D. Marjenberg1; P.J. Batstone2; K.E. Robertson1; D.A. Levison1; J.R. Goodlad1,3.
1. Division of Pathology and Neuroscience, University of Dundee, Dundee, United Kingdom
2. Department of Pathology, Raigmore Hospital, Inverness, United Kingdom
3. Department of Pathology, Western General Hospital, Edinburgh, United Kingdom

BACKGROUND: The characteristic genetic feature of follicular lymphoma (FL) is a t(14;18)(q32;q21) present in 85% of cases, leading to inhibition of apoptosis and an indolent phenotype. However, recent studies suggest that there may be a t(14;18)(q32;q21)-negative subgroup of FL that is more closely related to, and better treated as, diffuse large B-cell lymphoma (DLBCL). We sought to determine if there were genetic abnormalities to support such a hypothesis, by studying the genomic profile of a large cohort of t(14;18)(q32;q21)-positive and negative lymphomas of follicle centre origin.

METHODS: A combination of morphology, immunohistochemistry and fluorescence in situ hybridization was used to identify groups of translocation positive and negative FL, and DLBCL of germinal centre type.  Karyotypic analysis (N=100) and microarray-based comparative genomic hybridisation (aCGH) (N=40) were then used to determine the chromosomal aberrations in each group.

RESULTS: t(14;18)(q32;q21) positive and negative FL were found to have almost identical genetic profiles, with the exception of a loss of 1p36 found in 70% of t(14;18)(q32;q21) positive FL but only 10% of t(14;18)(q32;q21) negative FL.  A greater difference in chromosomal profiles was witnessed when t(14;18)(q32;q21) negative FL was compared with the cohort of DLBCL.

CONCLUSION: The results indicate that t(14;18)(q32;q21)-negative FL is genetically more closely related to t(14;18)(q32;q21)-positive FL than to DLBCL.  Further investigations are required to determine whether there are more subtle genetic abnormalities or epigenetic phenomena that might explain the pathogenesis of t(14;18)(q32;q21)-negative FL and account for the aggressive behaviour of a subset of cases.