Format

Send to

Choose Destination
Histopathology. 2015 Dec;67(6):843-58. doi: 10.1111/his.12714. Epub 2015 Jun 26.

Immunoglobulin rearrangement analysis from multiple lesions in the same patient using next-generation sequencing.

Author information

1
Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Core Unit Systems Medicine, University of Wuerzburg, Wuerzburg, Germany.
3
Department of Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Abstract

AIMS:

For patients who have multiple lymphomas with discordant pathology, it is relevant to determine whether there is one disseminated lymphoma or two unrelated lymphomas. Patients with disseminated, clonally related lymphomas are usually treated with the most powerful drugs available, while patients with unrelated (primary) lymphomas receive mainly standard first-line therapies.

METHODS AND RESULTS:

We used next-generation sequencing on the Ion Torrent Personal Genome Machine to characterize the immunoglobulin heavy gene V-D-J rearrangements in two diagnostic tissue samples, including formalin-fixed and paraffin-embedded tissue, of two patients with iatrogenic immunodeficiency-associated Epstein-Barr virus lymphoproliferative disorder, with ulcerative colitis as underlying disease. The immunoglobulin rearrangement sequences obtained by next-generation sequencing revealed undoubtedly clonally related lesions in two tissue biopsies that were taken over time in the first patient, which is concordant with disseminated lymphoma. The other patient showed two clonally unrelated lesions, which is incompatible with clonal dissemination. This information was not inferred from evaluation of the heavy and light chain rearrangements by fragment analysis, which is currently the gold standard.

CONCLUSION:

Our study demonstrates the diagnostic application of next-generation sequencing of immunoglobulin rearrangement assessment in pathology for clinical decision-making in patients with several simultaneous or subsequent lymphoproliferations.

KEYWORDS:

Epstein-Barr virus; Ion Torrent-PGM; immunoglobulin rearrangement; molecular pathology; ulcerative colitis

PMID:
25891511
DOI:
10.1111/his.12714
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center