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J Invest Dermatol. 2017 Sep;137(9):1984-1994. doi: 10.1016/j.jid.2017.04.010. Epub 2017 May 4.

Identification of Somatic Mutations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type by Massive Parallel Sequencing.

Author information

1
Department of Hematology, Henri Becquerel Comprehensive Cancer Center and Normandie Université, UNIROUEN, INSERM U1245, Team Genomics and biomarkers in lymphoma and solid tumors, Rouen, France.
2
Departments of Dermatology, Pathology, and Tumor Biology, CHU Bordeaux, Bordeaux, France; INSERM U1053, Team Oncogenesis of Cutaneous Lymphoma, University Bordeaux, Bordeaux, France.
3
Normandie Université, UNIROUEN, INSERM U1245 and Rouen University Hospital, Department of Genetics, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
4
Rouen University Hospital, Departments of Dermatology and Pathology, Rouen, France.
5
Department of Dermatology, Caen University Hospital, Caen, France.
6
Department of Hematology, Henri Becquerel Comprehensive Cancer Center and Normandie Université, UNIROUEN, INSERM U1245, Team Genomics and biomarkers in lymphoma and solid tumors, Rouen, France. Electronic address: fabrice.jardin@chb.unicancer.fr.

Abstract

To determine whether the mutational profile of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) is unique by comparison with other diffuse large B-cell lymphoma subtypes, we analyzed a total cohort of 20 PCLBCL-LT patients by using next-generation sequencing with a lymphoma panel designed for diffuse large B-cell lymphoma. We also analyzed 12 pairs of tumor and control DNA samples by whole-exome sequencing, which led us to perform resequencing of three selected genes not included in the lymphoma panel: TBL1XR1, KLHL6, and IKZF3. Our study clearly identifies an original mutational landscape of PCLBCL-LT with a very restricted set of highly recurrent mutations (>40%) involving MYD88 (p.L265P variant), PIM1, and CD79B. Other genes involved in B-cell signaling, NF-κB activation, or DNA modeling were found altered, notably TBL1XR1 (33%), MYC (26%) CREBBP (26%), and IRF4 (21%) or HIST1H1E (41%). MYD88L265P variant was associated with copy number variations or copy neutral loss of heterozygosity in 60% of patients. The most frequent genetic losses involved CDKN2A/2B, TNFAIP3/A20, PRDM1, TCF3, and CIITA. Together, these results show that PCLBCL-LT exhibits a unique mutational landscape, combining highly recurrent hotspot mutations in genes involved in NF-kB and B-cell signaling pathways, which provides a rationale for using selective inhibitors of the B-cell receptor.

PMID:
28479318
DOI:
10.1016/j.jid.2017.04.010
[Indexed for MEDLINE]
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