A novel missense (M206K) STAT3 mutation in diffuse large B cell lymphoma deregulates STAT3 signaling.

ABSTRACT: Persistent STAT3 activation has been found in activated B-cell like diffuse large B cell tumors (DLBCL). To investigate whether genetic mutations play a role in aberrant STAT3 signaling in DLBCL, we bi-directionally sequenced all 24 exons of the STAT3 gene in DLBCL tumors (n = 40). We identified 2 novel point mutations in 2 separate (2/40; 5%) patients at exon 7 and 24. Point mutation 2552G>A was a silent mutation in the stop codon. Another heterozygous mutation 857T>A encoded a methionine substitution by lysine at codon 206 (M206K) in the coiled-coil domain of STAT3. We performed site directed mutagenesis to mutate wild type (WT) STAT3α and STAT3β at codon 206 and constructed stable cell lines by lentiviral transfection of STAT3α(WT), STAT3α(M206K), STAT3β(WT) and STAT3β(M206K) plasmids.

SUBMITTER: Hu G 

PROVIDER: S-EPMC3701620 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature