Next generation sequencing of the clonal IGH rearrangement detects ongoing mutations and interfollicular trafficking in in situ follicular neoplasia

Perikles Kosmidis; Irina Bonzheim; Claudia Dufke; Sema Colak; Thomas Hentrich; Christopher Schroeder; Peter Bauer; Patrick Adam; Falko Fend

doi:10.1371/journal.pone.0178503

Next generation sequencing of the clonal IGH rearrangement detects ongoing mutations and interfollicular trafficking in in situ follicular neoplasia

PLoS One. 2017 Jun 22;12(6):e0178503. doi: 10.1371/journal.pone.0178503. eCollection 2017.

Authors

Perikles Kosmidis¹, Irina Bonzheim¹, Claudia Dufke², Sema Colak¹, Thomas Hentrich², Christopher Schroeder², Peter Bauer², Patrick Adam¹, Falko Fend¹

Affiliations

¹ Institute of Pathology and Neuropathology, Eberhard Karls University of Tübingen and Comprehensive Cancer Center, University Hospital Tübingen, Tübingen, Germany.
² Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany.

Abstract

Follicular lymphoma (FL) is characterized genetically by a significant intraclonal diversity of rearranged immunoglobulin heavy chain (IGH) genes and a substantial cell migration activity (follicular trafficking). Recently, in situ follicular neoplasia (ISFN), characterized by accumulations of immunohistochemically strongly BCL2-positive, t(14;18)+ clonal B cells confined to germinal centers in reactive lymph nodes, has been identified as a precursor lesion of FL with low risk of progression to manifest FL. The extent of ongoing somatic hypermutation of rearranged IGH genes and interfollicular trafficking in ISFN is not known. In this study we performed an in depth analysis of clonal evolution and cell migration patterns in a case of pure ISFN involving multiple lymph nodes. Using laser microdissection and next generation sequencing (NGS) we documented significant intraclonal diversity of the rearranged IGH gene and extensive interfollicular migration between germinal centers of the same lymph node as well as between different lymph nodes. Furthermore, we identified N-glycosylation motifs characteristic for FL in the CDR3 region.

MeSH terms

Aged
Cell Movement / genetics*
DNA Mutational Analysis*
Female
Gene Rearrangement*
High-Throughput Nucleotide Sequencing*
Humans
Immunoglobulin Heavy Chains / genetics*
Lymphoma, Follicular / genetics*
Lymphoma, Follicular / pathology*
Male

Substances

Immunoglobulin Heavy Chains

Grants and funding

This work was supported by the IZKF fortüne program (F14.63209), University of Tübingen (PA, https://www.medizin.uni-tuebingen.de/Forschung/Forschungsf%C3%B6rderung/Interne+Forschungsf%C3%B6rderung/Junior+Academy/fort%C3%BCne.html. PK and PA were in part supported by the Karl-Thiemig-Stiftung.