Long term impact and sustainability of our STEPUPIORS project surpass the official project end – the talented PhD student Xavi Dominguez-Rovira defended his PhD thesis mentored by Laia Bonjoch and Sergi Castellvi-Bel at FRCB-IDIBAPS. He was actively involved in project activities and presented his results at main consortium meetings during 2023-2025.
His thesis presents a multi-step approach for the postulation of HIC1 and TP53BP1 as candidate genes associated with germline predisposition to serrated polyposis syndrome (SPS). SPS patients, both with and without familial aggregation, were recruited into discovery and validation cohorts. Next-generation and panel sequencing were performed to identify germline pathogenic genetic variants, followed by a bioinformatics pipeline to prioritize the most relevant variants. CRISPR/Cas9 technology was used to model the identified genetic variants in several in vitro systems. These in vitro models were subsequently employed to conduct gene-specific functional assays to determine the effects of the genetic variants on RNA expression, protein function, and cellular processes. All data were integrated to support the candidacy of HIC1 and TP53BP1 as genes associated with germline predisposition to SPS.
https://onlinelibrary.wiley.com/doi/10.1002/ijc.35492
