Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2

Haematologica. 2018 Jul;103(7):1182-1190. doi: 10.3324/haematol.2017.181024. Epub 2018 Mar 22.

Abstract

A linear progression model of follicular lymphomas (FL) FL1, FL2 and FL3A has been favored, since FL3A often co-exist with an FL1/2 component. FL3B, in contrast, is thought to be more closely related to diffuse large B-cell lymphoma (DLBCL), and both are often simultaneously present in one tumor (DLBCL/FL3B). To obtain more detailed insights into follicular lymphoma progression, a comprehensive analysis of a well-defined set of FL1/2 (n=22), FL3A (n=16), FL3B (n=6), DLBCL/FL3B (n=9), and germinal center B-cell-type diffuse large B-cell lymphoma (n=45) was undertaken using gene expression profiling, immunohistochemical stainings and genetic analyses by fluorescence in situ hybridization. While immunohistochemical (CD10, IRF4/MUM1, Ki67, BCL2, BCL6) and genetic profiles (translocations of BCL2, BCL6 and MYC) delineate FL1-3A from FL3B and DLBCL/FL3B, significant differences were observed between FL1/2 and FL3A upon gene expression profiling. Interestingly, FL3B turned out to be closely related to FL3A, not categorizing within a separate gene expression cluster, and both FL3A and FL3B showed overlapping profiles in between FL1/2 and diffuse large B-cell lymphoma. Finally, based upon their gene expression pattern, DLBCL/FL3B represent a composite form of FL3B and DLBCL, with the majority of samples more closely resembling the latter. The fact that gene expression profiling clearly separated FL1/2 from both FL3A and FL3B suggests a closer biological relationship between the latter. This notion, however, is in contrast to immunohistochemical and genetic profiles of the different histological FL subtypes that point to a closer relationship between FL1/2 and FL3A, and separates them from FL3B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Computational Biology / methods
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genetic Association Studies*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lymphoma, Follicular / genetics*
  • Lymphoma, Follicular / pathology*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Transcriptome*

Substances

  • Biomarkers, Tumor