DNA methylation and copy number signatures in bone and soft tissue tumors: impact on classification and therapy response prediction
DNA methylation and copy number signatures in bone and soft tissue tumors:
Impact on classification and therapy response prediction
Bone and soft tissue tumors are rare and often difficult to diagnose. An accurate diagnosis is essential, as these tumors vary widely in clinical behavior and treatment. Therefore, cases are discussed in the multidisciplinary bone and soft tissue panel, where clinical information, imaging, and tissue analysis are integrated to achieve the most accurate diagnosis. Nevertheless, a definitive classification is not always possible, highlighting the need for additional diagnostic tools.
In this thesis of Tony Kleijn, he investigates two molecular techniques that may support this process: DNA methylation profiling and copy number variation (CNV) analysis. Although these methods are already successfully applied in the classification of brain tumors, they are still rarely used for bone and soft tissue tumors. Our research demonstrates that they also provide significant added value in this field.
We show that methylation and CNV profiles effectively distinguish benign fibro-osseous lesions from malignant osteosarcomas in the craniofacial bones. In addition, odontogenic myxomas were found to have a unique molecular profile, offering new insights into this rare benign jaw tumor.
We also demonstrate that atypical pleomorphic lipomatous tumors frequently harbor TP53 alterations, in contrast to spindle cell lipomas, and that methylation and CNV analysis assist in distinguishing these tumors from malignant liposarcomas.
Finally, these techniques have not only diagnostic but also prognostic utility. They improve risk stratification in patients with gastrointestinal stromal tumors, and a deletion on chromosome 11q24.1 appears to be a promising predictive marker for radiotherapy response in myxofibrosarcomas and undifferentiated pleomorphic sarcomas.