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Cancer Increase Reported in Families With Tau Mutation-Associated Neurodegeneration

NEW YORK (GenomeWeb) – A group of mutations most often associated with neurodegenerative conditions may also increase an individual's risk of developing cancer, new research suggests.

As they reported today in the journal Cancer Research, investigators from Italy and the UK did a retrospective analysis of more than a dozen frontotemporal lobar degeneration (FTLD)-prone families with documented tau gene mutations, collectively known as genetic tauopathies. Compared to unaffected control families, they saw an uptick in cancer diagnoses in the FTLD families, reflecting the chromosome instability that arises in the presence of tau mutations.

"Patients carrying tau mutations are usually attended for neurodegeneration," senior author Fabrizio Tagliavini, scientific director of Milan's IRCCS Foundation Carlo Besta Neurological Institute, said in a statement.

The tau gene codes for a microtubule-stabilizing protein that contributes to the cell's cytoskeleton, the team explained. Past studies have linked tau alterations to neurodegenerative conditions such as FTLD or Alzheimer's disease, though the protein's role in microtubule function also make it a likely contributor to successful cell division and chromosome stability — processes that often go awry in cancer.

"It is well-known that chromosome aberrations are often linked to cancer," Tagliavini added. "Therefore, we decided to determine if there was a possible association between tau mutations and cancer."

For their retrospective study, the researchers focused on 15 FTLD families made up of individuals carrying one of seven distinct pathogenic tau mutations, looking at how often cancer cases arose in individuals with FTLD, unaffected siblings, parents, aunts and uncles, and grandparents compared to comparable control families.

"For each tau-mutated family," the authors noted, "we collected data from [three] reference families with superimposable pedigrees, with a member born in the same year of the proband, of the same gender, and native Italian region."

Cases of cancer from several different types had been documented in 15 percent of individuals from the FTLD families, the researchers reported, compared with 9 percent of individuals in the matched control families.

The team's subsequent bioinformatic analysis also supported "a broader functional environment for the tau protein," Tagliavini explained, "which had been previously associated mainly with disease development in the context of neurodegeneration."

In particular, the researchers retraced the network of proteins that directly and indirectly interact with tau, highlighting sets of genes involved in everything from cytoskeleton dynamics to FNA damage, cell cycle checkpoints, chromosome segregation, and other processes that ensure appropriate chromosome segregation and stability. 

From these and other data, the authors concluded that "tau's functions go beyond assuring [microtubule] stability, as we demonstrate its nuclear involvement and association with genome stability and increased risk for cancer."

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