Panel Sequencing Shows Recurrent Genetic FAS Alterations in Primary Cutaneous Marginal Zone Lymphoma

The Journal of Investigative Dermatology
Katja MaurusM Wobser

Abstract

Primary cutaneous marginal zone lymphoma (PCMZL) represents an indolent subtype of non-Hodgkin lymphoma that is clinically characterized by slowly growing skin tumors with a very low propensity for systemic dissemination. The underlying genetic basis of PCMZL has not been comprehensively elucidated. To gain deeper insight into the molecular pathogenesis of PCMZL, we performed hybridization-based panel sequencing of 38 patients with well-characterized PCMZL. In 32 of the 38 patients, we identified genetic alterations within 39 selected target genes. The most frequently detected alterations (24/38 patients, 63.2%) affected the FAS gene, of which 22 patients harbored alterations, which affect the functionally relevant death domain of the apoptosis-regulating FAS/CD95 protein in a dominant-negative manner. In addition, we identified highly recurrent mutations in three other genes, namely SLAMF1, SPEN, and NCOR2. Our molecular data suggest that apoptosis defects provide the molecular basis of the observed clinical features of PCMZL, which commonly presents with only slowly growing skin tumors, reflecting its invariably indolent behavior. From a diagnostic point of view, highly recurrent FAS mutations in PCMZL presumably separate thi...Continue Reading

Citations

Jan 15, 2020·Der Pathologe·Marion Wobser, Matthias Goebeler
Oct 28, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Elaine S Jaffe
Sep 13, 2019·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·Marion Wobser, Matthias Goebeler
Nov 30, 2019·Virchows Archiv : an International Journal of Pathology·Ilske OschliesJohn R Goodlad
Aug 29, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Visar VelaThomas Menter
Aug 19, 2020·American Journal of Clinical Pathology·Sarah E Gibson, Steven H Swerdlow
Oct 13, 2020·Human Pathology·Nicholas J K BaraschSteven H Swerdlow
Dec 26, 2021·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Bryan ReaSarah E Gibson

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