Liquid biopsy for early tumor relapse detection : Development of hypersensitive genomic sequencing methodologies for the detection of ultra-rare genetic variants in the blood plasma of pediatric cancer patients

Rodríguez Sodupe, Pau

Liquid biopsy for early tumor relapse detection : Development of hypersensitive genomic sequencing methodologies for the detection of ultra-rare genetic variants in the blood plasma of pediatric cancer patients

Document Type

Doctoral thesis
Published Version

Author

Rodríguez Sodupe, Pau

Director

Rodríguez Lumbiarres, Jairo
Pérez Jurado, Luis Alberto

Publication Date

2022-03-09

Pages

236 p.

Citation

Rodríguez Sodupe, P. Liquid biopsy for early tumor relapse detection : Development of hypersensitive genomic sequencing methodologies for the detection of ultra-rare genetic variants in the blood plasma of pediatric cancer patients. 2022. handle: http://hdl.handle.net/10803/673741

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

The profiling of circulating-tumor DNA (ctDNA) in blood plasma, often known as liquid biopsy, has recently been of great interest in cancer research. This minimally-invasive strategy relies on the fact that ctDNA represents, at least partially, the real-time state of the tumor genome and holds great potential for early cancer detection and patient care. However, the fraction of ctDNA in total cell-free DNA (cfDNA) is often very low and requires ultra-sensitive and specific methods for its detection. This thesis focuses on the development and implementation of ultra-sensitive Next Generation Sequencing (NGS) methods that enable the identification of rare variants in plasma in a specific way. In summary, this work presents a comprehensive and cost-effective strategy for monitoring tumor mutations in the plasma of pediatric patients in a personalized manner. Our strategy aims to provide a tool to anticipate the detection and treatment of tumor relapses.
L’anàlisi d'ADN tumoral circulant (ADNtc) al plasma sanguini, sovint conegut com a biòpsia líquida, ha despertat recentment gran interès en la recerca del càncer. Aquesta estratègia mínimament invasiva es basa en que l’ADNtc representa, almenys parcialment, l'estat en temps real del genoma del tumor i té un gran potencial per a la detecció precoç del càncer. Tanmateix, la fracció d'ADNct en l'ADN lliure circulant (ADNlc) total és sovint molt baixa i es requereixen mètodes ultra-sensibles i específics per a la seva detecció. Aquesta tesi se centra en el desenvolupament i la implementació de mètodes ultra-sensibles basats en tecnologies de seqüenciació massiva (NGS) que permetin la identificació de variants rares en plasma de forma específica. En resum, aquest treball presenta una estratègia integral i rendible pel seguiment de mutacions tumorals en el plasma de pacients pediàtrics de manera personalitzada. La nostra estrategia pretén oferir una eina que permeti anticiparse en la detecció i tractament de recidives tumorals.

Keywords

ADN lliure circulant, Biòpsia líquida, Duplex Sequencing, Cáncer, Medicina personalitzada, Cellfree DNA, Liquid biopsy, Duplex Sequencing, Cancer, Personalized medicine