Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma
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Jochen K. Lennerz1,2,*, Karl Hoffmann1,3,*, Anna-Maria Bubolz1, Davor Lessel4,5, Claudia Welke6, Nele Rüther1, Andreas Viardot7, Peter Möller1
1Ulm University, Institute of Pathology, Ulm, Germany
2Massachusetts General Hospital/Harvard Medical School, Department of Pathology, Center for Integrated Diagnostics, Boston, MA, USA
3Department of Dermatology and Venerology, University of Freiburg Medical Center, Freiburg, Germany
4Ulm University, Institute of Human Genetics, Ulm, Germany
5University Medical Center Hamburg-Eppendorf, Institute of Human Genetics, Hamburg, Germany
6Comprehensive Cancer Center, Ulm University, Ulm, Germany
7Ulm University, Department of Internal Medicine III, Ulm, Germany
*These authors have contributed equally to this work
Jochen K. Lennerz, e-mail: JLennerz@partners.org
Keywords: SOCS1, Hodgkin lymphoma, cHL, prognostic biomarker
Received: April 02, 2015 Accepted: August 07, 2015 Published: August 20, 2015
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 multivariate analyses (P = 0.005). Together, our data indicate that the SOCS1 mutation type qualifies as a single-gene prognostic biomarker in cHL.
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