RESUMO
A novel allele HLA-B*56:31 differs from HLA-B*56:18 by three nucleotide substitutions resulting in a missense mutation Tyr171His (TAC to CAC) encoded in exon 3 and two silent substitutions at codon 188His (CAC to CAT) and codon 228Thr (ACT to ACC) encoded in exon 4.
Assuntos
Antígenos HLA-B/genética , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA/métodos , Alelos , Sequência de Bases , Humanos , Lituânia , Masculino , Dados de Sequência Molecular , Polimorfismo Genético , Homologia de SequênciaRESUMO
A novel allele HLA-C*07:185 differs from HLA-C*07:02 by a single nucleotide substitution that results in a missense mutation Ala 140 Pro (GCT to CCT) encoded in exon 3.
Assuntos
Alelos , Antígenos HLA-C/genética , Sequência de Bases , Códon , Éxons , Feminino , Variação Genética , Humanos , Lituânia , Modelos Genéticos , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNARESUMO
Nodal marginal zone lymphoma (NMZL) is a rare small B-cell lymphoma lacking disease-defining phenotype and precise diagnostic markers. To better understand the mutational landscape of NMZL, particularly in comparison to other nodal small B-cell lymphomas, we performed whole-exome sequencing, targeted high-throughput sequencing, and array-comparative genomic hybridization on a retrospective series. Our study identified for the first time recurrent, diagnostically useful, and potentially therapeutically relevant BRAF mutations in NMZL. Sets of somatic mutations that could help to discriminate NMZL from other closely related small B-cell lymphomas were uncovered and tested on unclassifiable small B-cell lymphoma cases, in which clinical, morphological, and phenotypical features were equivocal. Application of targeted gene panel sequencing gave at many occasions valuable clues for more specific classification.
Assuntos
Linfoma de Zona Marginal Tipo Células B/genética , Mutação/genética , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos RetrospectivosRESUMO
Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore, lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses to track tumors' genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally related relapses were detected as follows: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3-p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands the knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses.