Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• Desmoid tumors are locally aggressive fibroblastic neoplasms with high recurrence rates.
• Previous studies suggested transcriptomic signatures for relapse prediction.
• Molecular variability in desmoid tumors remains largely unexplored.

Purpose of the Study:

• To identify genes predictive of relapse in desmoid tumors through transcriptomic profiling.
• To investigate molecular variability within and between primary and recurrent desmoid tumors using multiomic analysis.

Main Methods:

• Transcriptomic profiling of 31 desmoid tumor specimens.
• Multiomic analysis (DNA methylation, copy-number alterations, mutations, gene expression) on 24 specimens from different tumor regions.
• Analysis of primary and recurrent tumors from three patients.

Main Results:

• Transcriptomic prognostic signatures showed high variability within individual tumors and between patients.
• Favorable and unfavorable outcome signatures were found in different regions of the same tumor.
• Remarkable intra- and intertumor heterogeneity in genomic, epigenomic, and transcriptomic patterns was observed.

Conclusions:

• Desmoid tumors display significant intra- and intertumor molecular heterogeneity.
• Single-biopsy molecular analysis may underestimate desmoid tumor alterations.
• Recurrent desmoid tumors acquire new molecular changes, emphasizing heterogeneity's role in drug development and biomarker validation.