Rossi, G;
Redaelli, V;
Contiero, P;
Fabiano, S;
Tagliabue, G;
Perego, P;
Benussi, L;
... Tagliavini, F; + view all
(2018)
Tau Mutations Serve as a Novel Risk Factor for Cancer.
Cancer Research
, 78
(13)
pp. 3731-3739.
10.1158/0008-5472.CAN-17-3175.
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Abstract
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.
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