Development and validation of a sequencing panel for translocations, copy number alterations and mutations with clinical relevance in mature B-Cell neoplasms
- Autores: Andrea Gomez Llonin
- Directores de la Tesis: Anna María Puiggros Metje (dir. tes.), Blanca Espinet Solà (dir. tes.), Bru Cormand Rifa (tut. tes.)
- Lectura: En la Universitat de Barcelona ( España ) en 2021
- Idioma: inglés
- Tribunal Calificador de la Tesis: Ana Batllé López (presid.), Raquel Rabionet Janssen (secret.), Rocío Nieves Salgado Sánchez (voc.)
- Programa de doctorado: Programa de Doctorado en Genética por la Universidad de Barcelona
- Materias:
- Enlaces
- Tesis en acceso abierto en: TDX
- Resumen
The application of NGS techniques to the study of mature B-cell neoplasms at the research level is providing a large amount of new information, in certain cases with clinical implications, which includes the identification of molecular biomarkers with diagnostic, prognostic and predictive value. The incorporation of some of these molecular biomarkers into clinical practice has shown to be crucial for the correct diagnosis and management of these patients. Therefore, the integration of molecular information together with the genetic alterations detectable by NGS is of main relevance in order to transfer the new genomic knowledge generated to daily clinical practice. However, withing the framework of mature B-cell neoplasms, the application of these techniques has been mainly focused on the description of somatic mutation profiles , which hinders their applicability to the daily clinical practice of these entities. In this sense, we have developed a targeted NGS panel that allows the study of genetic alterations with diagnostic, prognostic and therapeutic value in mature B-cell neoplasms, currently determined with different techniques, using a single methodology. In addition, the panel also includes other relevant genetic alterations, which may have an impact on the diagnostic routine in the near future and that, otherwise, would not be studied in the current clinical practice. Furthermore, to analyze the results obtained with the NGS panel, we have also designed a bioinformatic algorithm, which performs an integrative analysis using different bioinformatics tools. This approach allowed an increase in the specificity and sensitivity of the panel. In this sense, we have successfully validated most of the genomic alterations detected by the designed panel using different conventional genetic techniques (CBA, FISH, genomic microarrays, PCR and Sanger sequencing) in addition to other massive sequencing panels for SNV validation. Furthermore, this has allowed us to compare the sensitivity and specificity of the panel with respect to genetic techniques performed in routine laboratories in addition to other NGS panels. To our knowledge, this is the first panel developed that allows integrated analysis of SNV and small indels, CNA and chromosomal rearrangements in MBCN, and although some additional studies are required to improve its performance, the designed panel could potentially be implemented in clinical practice.
