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

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Department of Hematology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
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Institute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany
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Institute for Medical Informatics and Biometry, Faculty of Medicine Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany
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Department of Oral and Cranio-Maxillofacial Surgery, Kliniken Essen-Mitte, Evang. Huyssens-Stiftung/Knappschaft GmbH, University Hospital of Essen, 45136 Essen, Germany
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Department of Radiotherapy, University Hospital Essen, 45147 Essen, Germany
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Department of Ophthalmology, Molecular Ophthalmology Group, University of Duisburg-Essen, 45147 Essen, Germany
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German Cancer Consortium (DKTK), 45147 Essen, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 986; https://doi.org/10.3390/cancers12040986
Received: 10 March 2020 / Revised: 6 April 2020 / Accepted: 15 April 2020 / Published: 17 April 2020
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. View Full-Text
Keywords: ocular adnexal lymphoma; JAK/STAT; NOTCH; pathogenesis; somatic mutation ocular adnexal lymphoma; JAK/STAT; NOTCH; pathogenesis; somatic mutation
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MDPI and ACS Style

Johansson, P.; Klein-Hitpass, L.; Budeus, B.; Kuhn, M.; Lauber, C.; Seifert, M.; Roeder, I.; Pförtner, R.; Stuschke, M.; Dührsen, U.; Eckstein, A.; Dürig, J.; Küppers, R. Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing. Cancers 2020, 12, 986. https://doi.org/10.3390/cancers12040986

AMA Style

Johansson P, Klein-Hitpass L, Budeus B, Kuhn M, Lauber C, Seifert M, Roeder I, Pförtner R, Stuschke M, Dührsen U, Eckstein A, Dürig J, Küppers R. Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing. Cancers. 2020; 12(4):986. https://doi.org/10.3390/cancers12040986

Chicago/Turabian Style

Johansson, Patricia, Ludger Klein-Hitpass, Bettina Budeus, Matthias Kuhn, Chris Lauber, Michael Seifert, Ingo Roeder, Roman Pförtner, Martin Stuschke, Ulrich Dührsen, Anja Eckstein, Jan Dürig, and Ralf Küppers. 2020. "Identifying Genetic Lesions in Ocular Adnexal Extranodal Marginal Zone Lymphomas of the MALT Subtype by Whole Genome, Whole Exome and Targeted Sequencing" Cancers 12, no. 4: 986. https://doi.org/10.3390/cancers12040986

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