RESUMO
The pathogenesis of T-cell large granular lymphocytic leukemia (T-LGL) is poorly understood, as STAT3 mutations are the only known frequent genetic lesions. Here, we identified non-synonymous alterations in the TNFAIP3 tumor suppressor gene in 3 of 39 T-LGL. In two cases these were somatic mutations, in one case the somatic origin was likely. A further case harbored a SNP that is a known risk allele for autoimmune diseases and B cell lymphomas. Thus, TNFAIP3 mutations represent recurrent genetic lesions in T-LGL that affect about 8% of cases, likely contributing to deregulated NF-κB activity in this leukemia.
Assuntos
Proteínas de Ligação a DNA/genética , Variação Genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Leucemia Linfocítica Granular Grande/genética , Proteínas Nucleares/genética , Estudos de Coortes , Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA/metabolismo , Éxons , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Leucemia Linfocítica Granular Grande/metabolismo , Leucemia Linfocítica Granular Grande/patologia , Mutação , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT3/genética , Análise de Sequência de DNA , Proteína 3 Induzida por Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Characterization of novel fusion genes in acute leukemia is important for gaining information about leukemia genesis. We describe the characterization of a new ETV6 fusion gene in acute myeloid leukemia (AML) FAB M0 as a result of an uncommon translocation involving chromosomes 12 and 15. METHODS: The ETV6 locus at 12p13 was shown to be translocated and to constitute the 5' end of the fusion product by ETV6 break apart fluorescence in situ hybridisation (FISH). To identify a fusion partner 3' rapid amplification of cDNA-ends with polymerase chain reaction (RACE PCR) was performed followed by cloning and sequencing. RESULTS: The NTRK3 gene on chromosome 15 was found to constitute the 3' end of the fusion gene and the underlying ETV6-NTRK3 rearrangement was verified by reverse transcriptase PCR. No RNA of the reciprocal NTRK3-ETV6 fusion gene could be detected. CONCLUSION: We have characterized a novel ETV6-NTRK3 fusion transcript which has not been previously described in AML FAB M0 by FISH and RACE PCR. ETV6-NTRK3 rearrangements have been described in secretory breast carcinoma and congenital fibrosarcoma.