The gene that exacerbates blood cancer. TP53 is considered the “guardian of the genome” and is the most common mutated gene in cancer. The normal function of TP53 is to detect DNA damage and to prevent cells from transmitting this damage to daughter cells. When TP53 is mutated, the protein obtained from this gene, called p53, can no longer fulfill this protective function, and the result can be cancer. In many cancers, TP53 mutations are associated with poorer outcomes, such as disease recurrence and shorter survival.
As with all our genes, TP53 is found in duplicate in our cells. We get one copy from our mothers, the other from our fathers. To date, it has not been clear whether a mutation in one or both copies of TP53 is required to affect cancer outcome. A new study by researchers at Memorial Sloan Kettering certainly answers this question for a blood cancer called myelodysplastic syndrome (MDS), a precursor to acute myeloid leukemia.
“Our study is the first to assess the impact of the presence of a dysfunctional child on two TP53 children on cancer outcomes,”
She says the consequences for cancer diagnosis and treatment are immediate and profound.
A good definitive study
The study examined genetic and clinical data from 4,444 MDS patients treated in hospitals around the world.
Using new computational methods, the researchers found that approximately one-third of patients with MDS had only one mutated copy of TP53. These patients had similar results to patients who did not have a TP53 mutation – good response to treatment, low disease progression and better survival. On the other hand, two-thirds of the patients who had two mutated copies of TP53 had much worse outcomes, including treatment-resistant disease, rapid disease progression, and overall poor survival. In fact, the researchers found that the state of the TP53 mutation – zero, one or two mutated copies of the gene – was the most important variable to predict the outcome.
“Our results are of immediate clinical relevance to patients with MDS,” says Dr. Papaemmanuil. “Still, all patients with MDS should have TP53 status assessed at diagnosis.”