Tau Mutations Serve as a Novel Risk Factor for Cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 78; no. 13; pp. 3731 - 3739
• Main Authors: Rossi, Giacomina, Redaelli, Veronica, Contiero, Paolo, Fabiano, Sabrina, Tagliabue, Giovanna, Perego, Paola, Benussi, Luisa, Bruni, Amalia C., Filippini, Graziella, Farinotti, Mariangela, Giaccone, Giorgio, Buiatiotis, Simona, Manzoni, Claudia, Ferrari, Raffaele, Tagliavini, Fabrizio
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research, Inc 01.07.2018
• Subjects: Animal models; Bioinformatics; Cancer; Chromatin; Computational Biology; Female; Frontotemporal dementia; Frontotemporal Lobar Degeneration - genetics; Genetic Predisposition to Disease; Genomes; Genomic instability; Genomic Instability - genetics; Humans; Incidence; Male; Middle Aged; Mutation; Neoplasms - epidemiology; Neoplasms - genetics; Neurodegeneration; Neurodegenerative diseases; Pedigree; Protein Interaction Maps - genetics; Recombination; Retrospective Studies; Risk Factors; Tau protein; tau Proteins - genetics
• ISSN: 0008-5472; 1538-7445; 1538-7445
• DOI: 10.1158/0008-5472.CAN-17-3175

In addition to its well-recognized role in neurodegeneration, tau participates in maintenance of genome stability and chromosome integrity. In particular, peripheral cells from patients affected by frontotemporal lobar degeneration carrying a mutation in tau gene (genetic tauopathies), as well as cells from animal models, show chromosome numerical and structural aberrations, chromatin anomalies, and a propensity toward abnormal recombination. As genome instability is tightly linked to cancer development, we hypothesized that mutated tau may be a susceptibility factor for cancer. Here we conducted a retrospective cohort study comparing cancer incidence in families affected by genetic tauopathies to control families. In addition, we carried out a bioinformatics analysis to highlight pathways associated with the tau protein interactome. We report that the risk of developing cancer is significantly higher in families affected by genetic tauopathies, and a high proportion of tau protein interactors are involved in cellular processes particularly relevant to cancer. These findings disclose a novel role of tau as a risk factor for cancer, providing new insights in the various pathologic roles of mutated tau. Significance: This study reveals a novel role for tau as a risk factor for cancer, providing new insights beyond its role in neurodegeneration. Cancer Res; 78(13); 3731–9. ©2018 AACR.