Understanding the cancer-predisposing syndrome caused by defective proofreading activity of polymerases ε (POLE) and δ (POLD1)
Germline missense pathogenic variants in the exonuclease domains (ED) of polymerases epsilon (POLE) and delta (POLD1), which affect the proofreading capabilities of these polymerases, predispose to multiple colorectal adenomas and carcinomas, causing the so-called polymerase proofreading-associated polyposis (PPAP). The clinical characteristics of the syndrome and management of carriers, the molecular particularities of the associated tumors and their association with good prognosis and response to immunotherapy, and finally, the strategy proposed for the classification of variants identified in the genes, will be presented in the context of the studies performed by Laura Valle’s group.
Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Spain
Laura Valle, PhD, is a tenure-track (R3) researcher at IDIBELL. The research of her group is focused on the identification of the genetic causes of colorectal cancer predisposition, and the better characterization of new hereditary colorectal cancer and polyposis syndromes. In the past few years, her group has largely contributed to the clinical and molecular characterization of the polymerase proofreading-associated polyposis, caused by germline pathogenic variants in the exonuclease domains of POLE and POLD1; the NTHL1 tumor syndrome; and the RNF43-associated serrated polyposis. She carried out her PhD on hereditary nonpolyposis colorectal cancer at the Spanish Cancer Research Center (CNIO), after which she moved to Ohio State University as postdoctoral researcher under the supervision of Albert de la Chapelle. Since 2009 she leads her own research group, part of the Hereditary Cancer Program of the Catalan Institute of Oncology (ICO) – Bellvitge Biomedical Research Institute (IDIBELL).