MicroRNA expression in B-cell lymphomas

• Autores: Lorena di Lisio
• Directores de la Tesis: Miguel Ángel Piris Pinilla (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2012
• Idioma: español
• Tribunal Calificador de la Tesis: Juan Cruz Cigudosa García (presid.), Mercedes Robledo Batanero (secret.), Carlos Montalbán Sanz (voc.), Juan Fernando García García (voc.), José Antonio García Marco (voc.)
• Materias:
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: digitool-uam.greendata.es
• Resumen

  • Accurate lymphoma diagnosis, prognosis and therapy still require additional markers.

    Additionally, some aspects of lymphoma pathogenesis are still partially unexplained.

    In this work the potential relevance of microRNA (miRNA) expression in a large series of cases that included all major B-cell lymphoma types has been investigated.

    First, a series of 147 fresh frozen lymphomas and 15 controls were inspected for their miRNA expression profile. This analysis yielded a signature of 128 miRNAs that enabled the characterization of the different B-cell lymphoma types. Then a second series of cases was used to corroborate the differential expression of selected miRNAs vs. non-tumour controls.

    The viability of using miRNAs as additional markers for differential diagnosis has been investigated by comparing Burkitt Lymphoma (BL) vs. Diffuse Large B-cell Lymphoma (DLBCL) and resulted in the identification of 19 significant miRNAs (False Discovery Rate < 0.05).

    Not only: the correlation between miRNA expression profiles, gene expression profiles and pathway activation was examined in Mantle Cell Lymphoma (MCL), suggesting the implication of different miRNAs in pathway regulation. In particular, loss of miR-26a may contribute to NFkB pathway activation.

    Furthermore the clinical prognostic value of miRNAs has been examined in MCL cases, where miR-20b was identified as a good candidate for overall survival stratification of the patients.

    Finally, selected miRNAs were sequenced to test the presence and the relevance of miRNA sequence variation in a series of 95 DLBCL cases.

    In summary this work identifies good candidate miRNAs that might be used to better recognise the different B-cell lymphoma types (especially BL and DLBCL), and other miRNAs that could contribute to lymphoma pathogenesis elucidation.