TY - JOUR
T1 - New Insights Into the Complex Mutational Landscape of Sézary Syndrome
AU - Mirza, Abu Sayeef
AU - Horna, Pedro
AU - Teer, Jamie K.
AU - Song, Jinming
AU - Akabari, Ratilal
AU - Hussaini, Mohammad
AU - Sokol, Lubomir
N1 - Publisher Copyright:
© Copyright © 2020 Mirza, Horna, Teer, Song, Akabari, Hussaini and Sokol.
PY - 2020/4/21
Y1 - 2020/4/21
N2 - Sézary syndrome (SS) is a genetically and clinically distinct entity among cutaneous T-cell lymphomas (CTCL). SS is characterized by more aggressive disease compared to the most common indolent type of CTCL, mycosis fungoides. However, there are limited available genomic data regarding SS. To characterize and expand current mappings of the genomic landscape of CTCL, whole exome sequencing (WES) was performed on peripheral blood samples from seven patients with SS. We detected 21,784 variants, of which 21,140 were novel and 644 were previously described. Filtering revealed 551 nonsynonymous variants among 525 mutated genes−25 recurrent mutations and 1 recurrent variant. Several recurrently mutated genes crucial to pathogenesis pathways, including Janus kinase (JAK)/signal transducers and activators of transcription (STAT), peroxisome proliferator-activated receptors (PPAR), PI3K-serine/threonine protein kinases (AKT), and fibroblast growth factor receptors (FGFR), were identified. Furthermore, genetic mutations spanned both known and novel genes, supporting the idea of a long-tail distribution of mutations in lymphoma. Acknowledging these genetic variants and their affected pathways may inspire future targeted therapies. WES of a limited number of SS patients revealed both novel findings and corroborated complexities of the “long-tail” distribution of previously reported mutations.
AB - Sézary syndrome (SS) is a genetically and clinically distinct entity among cutaneous T-cell lymphomas (CTCL). SS is characterized by more aggressive disease compared to the most common indolent type of CTCL, mycosis fungoides. However, there are limited available genomic data regarding SS. To characterize and expand current mappings of the genomic landscape of CTCL, whole exome sequencing (WES) was performed on peripheral blood samples from seven patients with SS. We detected 21,784 variants, of which 21,140 were novel and 644 were previously described. Filtering revealed 551 nonsynonymous variants among 525 mutated genes−25 recurrent mutations and 1 recurrent variant. Several recurrently mutated genes crucial to pathogenesis pathways, including Janus kinase (JAK)/signal transducers and activators of transcription (STAT), peroxisome proliferator-activated receptors (PPAR), PI3K-serine/threonine protein kinases (AKT), and fibroblast growth factor receptors (FGFR), were identified. Furthermore, genetic mutations spanned both known and novel genes, supporting the idea of a long-tail distribution of mutations in lymphoma. Acknowledging these genetic variants and their affected pathways may inspire future targeted therapies. WES of a limited number of SS patients revealed both novel findings and corroborated complexities of the “long-tail” distribution of previously reported mutations.
KW - Sézary syndrome
KW - cutaneous T-cell lymphoma
KW - genomics
KW - translational oncology
KW - whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85084251952&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084251952&partnerID=8YFLogxK
U2 - 10.3389/fonc.2020.00514
DO - 10.3389/fonc.2020.00514
M3 - Article
AN - SCOPUS:85084251952
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 514
ER -