The TP53 gene codes for p53, an important tumor suppressor protein. Germline mutations in this gene cause Li-Fraumeni syndrome, characterized by a high risk of developing different types of cancer from childhood. The main tumors associated with this syndrome are sarcomas, osteosarcomas, breast and brain tumors, and adrenocortical carcinomas.

Currently, the genetic diagnosis of patients with familial cancer is performed by the sequencing of a broad panel of genes. The implementation of these panels in clinical practice has permitted the detection of mutations in the TP53 gene in a much larger range of patients. This fact has revealed that some patients without the clinical characteristics of Li-Fraumeni syndrome presented pathogenic mutations in the TP53 gene. This could be due to the conservation of these mutations in the genome of some individuals without functional transcendence, or maybe the mutations of the TP53 gene could be implicated in the development of colon cancer in the absence of a clear clinical phenotype of Li-Fraumeni.

In order to decipher the real implication of germline mutations in the TP53 gene in colon cancer, the team of Dr. Laura Valle, from the hereditary cancer group of the Bellvitge Biomedical Research Institute (IDIBELL) and the Institute Catalan of Oncology (ICO), has studied the frequency and nature of these mutations.

To do that, they have analyzed the TP53 gene in up to 6,200 samples from patients with colon cancer and, they have compared the results with the same analyzes done in individuals without cancer and in patients with Li-Fraumeni syndrome. The study, published in the journal Gut, reveals that colon cancer patients have a higher frequency of mutations than healthy patients, meanly mutations that affect the protein function, which would mean that the mutations in this gene could predispose to colorectal cancer.

“We should not associate pathogenic mutations of the TP53 gene with Li Fraumeni syndrome in all cases,” says Dr. Valle, leader of the project. And she adds, “The connection between these mutations and colon cancer raises important questions about risk estimation, follow-up and clinical management of carriers of TP53 mutations who do not develop the syndrome from a clinical point of view. A detailed follow-up of these patients is essential to define the management of these patients”.