Genomic study identifies patients with rare tumor at higher risk of metastasis

Pheochromocytoma is a rare tumor, with an annual incidence of three to eight cases per million inhabitants. This week the largest study on its molecular causes is published in Nature Communications and focused on patients with metastatic pheochromocytomas, which represent 20% of all cases. Survival of patients with this type of tumor is 20% to 60% in five years.

One of the two researchers who led the work is Mercedes Robledo, head of the Hereditary Endocrine Cancer Group at the National Cancer Research Center (CNIO). Robledo has dedicated himself to the study of these tumors since 1996: “One of the difficulties of working with rare diseases is recruiting large series of patients that allow robust conclusions. And this study stands out because the number of samples we worked with is exceptional.”

The number of patients with metastatic disease included in our study corresponds to a population of one hundred million people.

Bruna Calsina, research co-author

To understand the magnitude of the study, the co-author and CNIO researcher, Bruna Calsina, explains: “The number of patients with metastatic disease in our study corresponds to a population of one hundred million people”.

This was possible thanks to the collaboration between 16 reference centers for the study of the disease in six countries around the world, with which the CNIO Group has been working for a decade.

Bookmarks for a more personalized approach

Such a large sample was needed to achieve what they and their research colleagues achieved with their work: identifying, at the time of diagnosis of the primary tumor, markers associated with an increased risk of metastasis. These markers can be added to other clinical and histological criteria for personalized clinical management.

As Robledo and Calsina explain, most patients with this type of tumor who develop metastases do so one or two years after the disease is diagnosed, but there are cases in which the metastasis develops ten or twenty years after the initial diagnosis.

New molecular markers will help clinicians monitor patients at high risk for metastasis more closely

The new molecular markers will help responsible physicians more closely monitor patients at high risk for metastasis.

Response to immunotherapy

Another problem with this rare disease is that therapies don’t always work, and the reason is unknown. “This is a hereditary disease in 40% or 50% of cases -Robledo explains-, and very complex from a genetic point of view. Up to 22 disease-related genes have been identified, of which five were discovered in our lab.”

The more genes involved in a disease, the more difficult it is to study and the more complex it is to find effective therapies. So far, several types of treatments have been tested, from chemotherapy to targeted therapies, but, as Calsina explains, “it is not known a priori which patients may respond to one or another therapy”.

Therefore, another part of the research consisted of looking for markers that would allow the personalization of the treatment. The work identified a group of patients with pheochromocytoma who could benefit from immunotherapy treatments.


Calsina B, Piñeiro-Yáñez E, Martínez-Montes ÁM. et al. “Genomic and immune landscape of metastatic pheochromocytoma and paraganglioma”. Nat Commun (February 2023)

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