RESUMO
Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing. Common mutated genes were BRAF (29%), NRAS (28%), ALK, KIT, and MAP2K1 (5% each). Co-occurring mutations were detected in 29% of the samples, including BRAF with KIT, CTNNB1, EGFR, ALK, HRAS, or MAP2K1. Amplifications and rearrangements were detected in 5% of cases. Only BRAF mutation showed a significant statistical association with sun exposure. For patients with a given genetic profile, the melanoma survival and recurrence-free survival rates were equivalent, but not for stage and LDH values. This expanded knowledge of molecular alterations has helped to more comprehensively characterize our patients and has provided relevant information for deciding the best treatment strategy.
Assuntos
Melanoma , Mutação , Humanos , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Espanha , Adulto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Proteínas Proto-Oncogênicas B-raf/genética , Biomarcadores Tumorais/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.
Assuntos
Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Membrana Sinovial , Linfócitos B , Fator de Necrose Tumoral alfa , FenótipoRESUMO
El diagnóstico prenatal citogenético durante el primer trimestre de gestación se realiza a partir de biopsias de vellosidad corial. Para la obtención de metafases se utilizan dos métodos: el cultivo corto o semidirecto (STC) y cultivo largo (LTC). La principal ventaja del STC es que no presenta contaminación materna y la del LTC es que no hay descritos en la literatura falsos negativos. Se considera que la combinación de las dos técnicas (STC y LTC) es la estrategia diagnóstica más eficaz para este tipo de estudios. La técnica de PCR cuantitativa fluorescente (QF-PCR) permite evaluar las aneuploidías más frecuentemente implicadas en el diagnóstico prenatal en 24-48 horas en muestras de vellosidad corial. El objetivo de este trabajo es evaluar la combinación de QF-PCR y LTC como sustituto de las clásicas STC y LTC para el diagnóstico prenatal en muestras de vellosidad corial. Para ello presentamos nuestra experiencia en 900 muestras de vellosidad corial(AU)
First trimester cytogenetic prenatal diagnosis is performed on chorionic villus biopsies. Two methods are used to obtain metaphases: the short-term or semi-direct culture (STC) and long term culture (LTC). The main advantage of STC is that there is no risk of maternal contamination, and of LTC that no false-negative findings are described in the literature. It is considered that the combination of the two techniques (STC and LTC) is the most effective diagnostic strategy for this type of study. The technique of quantitative fluorescent PCR (QF-PCR) allows the evaluation of aneuploidy most frequently involved in prenatal diagnosis in 24-48 hours in chorionic villus samples. The aim of this study is to evaluate the combination of QF-PCR and LTC as a substitute for classical STC and LTC for prenatal diagnosis in chorionic villus samples. We present our experience in 900 chorionic villus samples(AU)