Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing

Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung

Beitragende

  • Patricia Johansson - , Universitätsklinikum Essen (Autor:in)
  • Ludger Klein-Hitpass - , Universität Duisburg-Essen (Autor:in)
  • Bettina Budeus - , Universität Duisburg-Essen (Autor:in)
  • Matthias Kuhn - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Chris Lauber - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Michael Seifert - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Ingo Roeder - , Institut für Medizinische Informatik und Biometrie (Autor:in)
  • Roman Pförtner - , Universitätsklinikum Essen (Autor:in)
  • Martin Stuschke - , Universitätsklinikum Essen (Autor:in)
  • Ulrich Dührsen - , Universitätsklinikum Essen (Autor:in)
  • Anja Eckstein - , Universität Duisburg-Essen (Autor:in)
  • Jan Dürig - , Universitätsklinikum Essen, Deutsches Konsortium für Translationale Krebsforschung (DKTK) - Dresden (Autor:in)
  • Ralf Küppers - , Universität Duisburg-Essen, Deutsches Konsortium für Translationale Krebsforschung (DKTK) - Heidelberg (Autor:in)

Abstract

The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is not fully understood. We performed whole genome sequencing (WGS) and/or whole exome sequencing (WES) for 13 cases of OAML and sequenced 38 genes selected from this analysis in a large cohort of 82 OAML. Besides confirmation of frequent mutations in the genes transducin beta like 1 X-linked receptor 1 (TBL1XR1) and cAMP response element binding protein (CREBBP), we newly identifed JAK3 as a frequently mutated gene in OAML (11% of cases). In our retrospective cohort, JAK3 mutant cases had a shorter progression-free survival compared with unmutated cases. Other newly identified genes recurrently mutated in 5-10% of cases included members of the collagen family (collagen type XII alpha 1/2 (COL12A1, COL1A2)) and DOCK8. Evaluation of the WGS data of six OAML did not reveal translocations or a current infection of the lymphoma cells by viruses. Evaluation of the WGS data for copy number aberrations confirmed frequent loss of TNFAIP3, and revealed recurrent gains of the NOTCH target HES4, and of members of the CEBP transcription factor family. Overall, we identified several novel genes recurrently affected by point mutations or copy number alterations, but our study also indicated that the landscape of frequently (>10% of cases) mutated protein-coding genes in OAML is now largely known.

Details

OriginalspracheEnglisch
Aufsatznummer986
FachzeitschriftCancers
Jahrgang12
Ausgabenummer4
PublikationsstatusVeröffentlicht - 17 Apr. 2020
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC7225979
Scopus 85083961434
ORCID /0000-0002-2844-053X/work/153655328
ORCID /0000-0003-2868-5155/work/199962753
ORCID /0000-0002-6741-0608/work/199962894

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