Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma.
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.
Ulm University, Institute of Pathology, Ulm, Germany.|Massachusetts General Hospital/Harvard Medical School, Department of Pathology, Center for Integrated Diagnostics, Boston, MA, USA.
Jochen K
JK
Lennerz
Ulm University, Institute of Pathology, Ulm, Germany.|Department of Dermatology and Venerology, University of Freiburg Medical Center, Freiburg, Germany.
Karl
K
Hoffmann
Ulm University, Institute of Pathology, Ulm, Germany.
Anna-Maria
AM
Bubolz
Ulm University, Institute of Human Genetics, Ulm, Germany.|University Medical Center Hamburg-Eppendorf, Institute of Human Genetics, Hamburg, Germany.
Davor
D
Lessel
Comprehensive Cancer Center, Ulm University, Ulm, Germany.
Claudia
C
Welke
Ulm University, Institute of Pathology, Ulm, Germany.
Nele
N
Rüther
Ulm University, Department of Internal Medicine III, Ulm, Germany.
Andreas
A
Viardot
Ulm University, Institute of Pathology, Ulm, Germany.
Peter
P
Möller
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016009:Chi-Square Distribution; D002648:Child; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006689:Hodgkin Disease / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D016016:Proportional Hazards Models; D012008:Recurrence; D016539:Reed-Sternberg Cells / Q000737:chemistry / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D014408:Biomarkers, Tumor; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
Hodgkin lymphoma; SOCS1; cHL; prognostic biomarker