Large international study pinpoints impact of TP53 gene muta
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Up until now, it has not been clear whether a mutation was needed in one or both copies of TP53 to affect cancer outcomes. A new study led by researchers definitively answers this question for a blood cancer called myelodysplastic syndrome (MDS), a precursor to acute myeloid leukemia.

This study is the first to assess the impact of having one versus two dysfunctional copies of TP53 on cancer outcomes," says researchers in a study published in the journal Nature Medicine. "From these results, it's clear that you need to lose function of both copies to see evidence of genome instability and a high-risk clinical phenotype in MDS."

The study analyzed genetic and clinical data from 4,444 patients with MDS who were being treated at hospitals all over the world. Using new computational methods, the investigators found that about one-third of MDS patients had only one mutated copy of TP53. These patients had similar outcomes as patients who did not have a TP53 mutation—a good response to treatment, low rates of disease progression, and better survival rates.

On the other hand, the two-thirds of patients who had two mutated copies of TP53 had much worse outcomes, including treatment-resistant disease, rapid disease progression, and low overall survival. In fact, the researchers found that TP53 mutation status—zero, one, or two mutated copies of the gene—was the most important variable when predicting outcomes.

"These findings are of immediate clinical relevance to MDS patients," researchers say. "Going forward, all MDS patients should have their TP53 status assessed at diagnosis."

Source: https://www.nature.com/articles/s41591-020-1008-z
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