Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma
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Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma. / Lennerz, Jochen K; Hoffmann, Karl; Bubolz, Anna-Maria; Lessel, Davor; Welke, Claudia; Rüther, Nele; Viardot, Andreas; Möller, Peter.
In: ONCOTARGET, Vol. 6, No. 30, 06.10.2015, p. 29097-110.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma
AU - Lennerz, Jochen K
AU - Hoffmann, Karl
AU - Bubolz, Anna-Maria
AU - Lessel, Davor
AU - Welke, Claudia
AU - Rüther, Nele
AU - Viardot, Andreas
AU - Möller, Peter
PY - 2015/10/6
Y1 - 2015/10/6
N2 - 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.
AB - 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.
U2 - 10.18632/oncotarget.4829
DO - 10.18632/oncotarget.4829
M3 - SCORING: Journal article
C2 - 26336985
VL - 6
SP - 29097
EP - 29110
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 30
ER -