Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma

Oncotarget
Jochen K LennerzP Möller

Abstract

Suppressor of cytokine signaling 1 (SOCS1) mutations are among the most frequent somatic mutations in classical Hodgkin lymphoma (cHL), yet their prognostic relevance in cHL is unexplored. Here, we performed laser-capture microdissection of Hodgkin/Reed-Sternberg (HRS) cells from tumor samples in a cohort of 105 cHL patients. Full-length SOCS1 gene sequencing showed mutations in 61% of all cases (n = 64/105). Affected DNA-motifs and mutation pattern suggest that many of these SOCS1 mutations are the result of aberrant somatic hypermutation and we confirmed expression of mutant alleles at the RNA level. Contingency analysis showed no significant differences of patient-characteristics with HRS-cells containing mutant vs. wild-type SOCS1. By predicted mutational consequence, mutations can be separated into those with non-truncating point mutations ('minor' n = 49/64 = 77%) and those with length alteration ('major'; n = 15/64 = 23%). Subgroups did not differ in clinicopathological characteristics; however, patients with HRS-cells that contained SOCS1 major mutations suffered from early relapse and significantly shorter overall survival (P = 0.03). The SOCS1 major status retained prognostic significance in uni-(P = 0.016) and multiv...Continue Reading

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Citations

Jun 16, 2016·British Journal of Haematology·Jochen K LennerzUNKNOWN network project Molecular Mechanisms in Malignant Lymphomas
Aug 23, 2019·Leukemia·Ann-Kathrin DeschAndreas Bräuninger
Aug 14, 2019·British Journal of Haematology·Kevin MellertPeter Möller
Jul 19, 2017·Cold Spring Harbor Perspectives in Biology·Akihiko YoshimuraHiroko Nakatsukasa
May 19, 2019·Cancer Research·Emmanuelle Saint-GermainGerardo Ferbeyre
Mar 14, 2021·European Journal of Haematology·Stephanie E WeissingerPeter Möller
Aug 21, 2021·International Immunology·Akihiko YoshimuraMakoto Ando

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Methods Mentioned

BETA
PCR
laser
genotyping
biopsy
laser-capture microdissection
flow-cytometry
electrophoresis

Clinical Trials Mentioned

NCT01505712

Software Mentioned

KB
ChromasPro
GraphPad Prism
MacSequenceView
R package
[UNK] Base Caller
Sequencing Analysis Software

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