title: Immunoglobulin rearrangement analysis from multiple lesions in the same patient using next-generation sequencing.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.|Core Unit Systems Medicine, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Appenzeller
authors.affiliation: Department of Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Gilissen
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Rijntjes
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bastiaan B J
authors.initials: BB
authors.lastname: Tops
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Annemiek
authors.initials: A
authors.lastname: Kastner-van Raaij
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Konnie M
authors.initials: KM
authors.lastname: Hebeda
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Loes
authors.initials: L
authors.lastname: Nissen
authors.affiliation: Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bas E
authors.initials: BE
authors.lastname: Dutilh
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J Han J M
authors.initials: JH
authors.lastname: van Krieken
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
mesh_terms: D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008223:Lymphoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007143:Immunoglobulin Heavy Chains
keywords: Epstein-Barr virus; Ion Torrent-PGM; immunoglobulin rearrangement; molecular pathology; ulcerative colitis