Study uncovers surprising molecular diversity in desmoid tumours, challenging previous assumptions and opening the door to more personalized care

SOURCE: The Research Institute McGill University Health Centre (The Institute)
May 1, 2025

A new study published in Clinical Cancer Research and led by researchers at the Research Institute of the McGill University Health Centre (The Institute) has revealed an unexpected level of molecular heterogeneity in desmoid tumours, a rare and potentially life-threatening type of soft tissue tumour. The findings challenge previous assumptions about the uniform nature of these tumours and may lead to more personalized treatment strategies.

Desmoid tumours are rare, affecting approximately 5 to 6 people per million each year. They arise from fibroblasts—the cells that form connective tissue—and can develop in various parts of the body, most commonly in the abdomen, arms or legs. Although they do not spread to distant organs, they can invade nearby tissues, sometimes resulting in serious complications or even death.

"We became interested in the molecular complexity of desmoid tumours because of their unpredictable behavior in patients," said Joanna Przybyl, PhD, senior author of the study, Junior Scientist in the Cancer Research Program at The Institute, and Assistant Professor in the Department of Surgery at McGill University. "Some tumours remain stable or regress, while others grow aggressively and require intensive treatment."

Historically, the uniform shape and growth pattern observed in microscopic analyses of desmoid tumours led researchers to believe these tumours were relatively homogeneous. As a result, they were not previously suspected to exhibit the kind of molecular heterogeneity commonly seen in more aggressive cancers.

This study is the first to apply high-dimensional molecular profiling techniques to the characterization of desmoid tumours. The research team used a comprehensive approach, integrating genomic, epigenomic, and transcriptomic data from tumour samples.

The researchers discovered significant molecular heterogeneity within individual tumours. This suggests that a standard tissue biopsy—typically taken from a single tumour region—may not fully represent the molecular landscape of the entire tumour, which could influence treatment decisions.

The study also showed for the first time that desmoid tumours which recur after surgery might evolve molecularly, developing new characteristics that could require different treatment approaches than the original tumour.

"These findings suggest that more tailored diagnostic and therapeutic strategies may be warranted in the future," said Chelsea De Bellis, first author of the study and a Master's student in Prof. Przybyl's lab at the time of this work.

About the study

"Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors" by Chelsea De Bellis, Sujay Vennam, Christopher Eeles, Pegah Rahimizadeh, Justin Cates, Thomas Stricker, Jenny Hoffman, Kristen Ganjoo, Gregory W. Charville, Benjamin Haibe-Kains, Matt van de Rijn and Joanna Przybyl was published in Clinical Cancer Research. This was a collaborative study by scientists and clinicians from The Institute, McGill University, Stanford University, Vanderbilt University and the University of Toronto.

DOI: 10.1158/1078-0432.CCR-24-1240

This work was supported by The Desmoid Tumor Research Foundation (USA) and The Desmoid Tumour Foundation of Canada.