TP53 Mutation Status Linked to Patient Outcome

An international, genetic association study led by Memorial Sloan Kettering demonstrates a link between TP53 genome stability and the clinical presentation and outcomes in myelodysplastic syndromes (MDS). Their results were published today in Nature Medicine.

"Our study is the first to assess the impact of having one versus two dysfunctional copies of TP53 on cancer outcomes," says lead scientist Elli Papaemmanuil. "From our 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 applications for cancer diagnosis and treatment could be immediate, she says. 

The team analyzed genetic and clinical data from 4,444 patients with myelodysplastic syndrome (MDS) who were being treated in hospitals all over the world. Existing guidelines do not consider genomic data and other acquired mutations when determining treatment or assessing prognosis. “That needs to change,” says co-author Peter Greenberg. 

Through computational methods and analyses, the team identified that TP53 mutation status was the most important variable when predicting outcomes. While patients who expressed one or no mutated copy of TP53 shared disease prognosis—and survival rates—those who had two dysfunctional copies also shared clinical outcomes.

Their findings highlight the importance to study these molecular differences in relation to other types of cancer. "With the increasing adoption of molecular profiling at the time of cancer diagnosis, we need large, evidence-based studies to inform how to translate these molecular findings into optimal treatment strategies," Papaemmanuil concludes.