May 05, 2026
Molecular-driven classification is rapidly reshaping diagnostic protocols in pediatric oncology, with a well-established impact in leukemias and brain tumors. A similar shift is occurring in soft tissue sarcomas. Tumor genomic profiling is playing an increasingly central role, particularly in non-rhabdomyosarcoma soft tissue sarcomas (NRSTS).
"What we learn through molecular testing is now driving the diagnosis and management of many solid tumors," says Wendy A. Allen-Rhoades, M.D., Ph.D., a pediatric hematologist/oncologist at Mayo Clinic Children's in Rochester, Minnesota. "In soft tissue sarcoma, identifying underlying genetic alterations enables us to more precisely classify tumors and individualize treatment strategies."
Role of genomic assays in diagnosing pediatric soft tissue sarcoma
Genomic profiling provides critical insights that can significantly influence diagnostic accuracy and therapeutic decisions for many soft tissue sarcoma subtypes. But Dr. Allen-Rhoades says its impact is particularly profound in NRSTS.
The diverse histologic subtypes that make up pediatric NRSTS have traditionally been managed with largely standardized, one-size-fits-all approaches. Limitations in classification have hindered precise treatment and individualized risk assessment. Genomic profiling is reshaping that landscape, as genetic alterations now define many soft tissue sarcomas.
"We incorporate genomic profiling when it is clinically indicated to help with the diagnosis," Dr. Allen-Rhoades says. "Establishing an accurate diagnosis remains the most critical step, as it fundamentally directs clinical decision-making and shapes therapeutic strategy. Molecular subtyping further refines this process. In some cases, it informs targeted treatment selection. In others, it clarifies or even redefines the underlying diagnosis, deepening our understanding of disease biology and supporting more precise management."
At Mayo Clinic Children's, decisions regarding genomic testing of primary tumors are tumor dependent and typically initiated by specialized pathologists involved with the pediatric sarcoma program. Close collaboration between oncologists and pathologists facilitates detailed interpretation and contextual reporting.
Tumor profiling of relapsed and metastatic NRSTS also provides important clinical value, particularly in guiding subsequent treatment strategies.
"Analysis of the relapse specimen may demonstrate tumor evolution caused by selective pressure associated with prior therapy," Dr. Allen-Rhoades says. "It may also reveal new genetic alterations that are therapeutically exploitable."
Molecular profiling of metastatic lesions helps determine concordance with the primary tumor. It also may reveal adaptation acquired during metastatic progression, which can influence the treatment approach.
How molecular testing informs treatment in soft tissue sarcomas
Some genetic alterations in soft tissue sarcomas can be addressed with tissue-agnostic targeted therapies, which focus on a tumor's molecular markers instead of its anatomical location or tissue type. But, in most cases, clinicians use genomic profiling to clarify the biologic behavior of a tumor.
"We incorporate targeted medication into the treatment plan, if one exists for that genetic change," Dr. Allen-Rhoades says. "But actionable alterations that we can act upon for therapy are the minority for soft tissue sarcoma."
In the absence of a targetable alteration, clinicians must focus on understanding the downstream biological effects of a molecular change and identifying therapeutic vulnerabilities.
"If we cannot directly target that primary driver of tumor behavior, we need to understand all the ancillary ways it is affecting tumor growth," Dr. Allen-Rhoades says. She references Ewing sarcoma as an example. "We've known what causes Ewing sarcoma for decades, yet we have not been able to target the genetic change directly. However, treatment strategies can instead focus on downstream proteins or pathways activated by that alteration."
Addressing challenges in pediatric tumor genomic profiling
Historically, implementation of tumor genomic profiling in pediatric oncology has often been constrained by limitations, including:
- Insufficient representation of pediatric-specific alterations in available testing panels.
- Limited DNA in small biopsy specimens, specifically core needle samples.
- Prolonged turnaround time associated with sending specimens to an outside lab.
In-house molecular diagnostics through Mayo Clinic Laboratories mitigates these issues, offering a comprehensive suite of testing modalities, including:
- Next-generation sequencing of RNA and DNA.
- Paired tumor-germline analysis.
To ensure that tumor assays reflect current pediatric oncology needs, the MayoComplete Solid Tumor Panel was developed in collaboration with Mayo Clinic Children's pediatric oncology specialists. The panel detects gene fusions and other molecular alterations associated with pediatric cancer, which are often underrepresented in commercially available panels designed for adult cancers.
Performing molecular testing in-house substantially reduces turnaround time and eliminates delays associated with sending out tissue samples. Results from the solid tumor complete panel are typically available in about 10 days. If the tissue sample yields insufficient DNA, access to additional tumor cells is available to enable additional analysis.
"Specimen size is frequently limited in core needle biopsies," Dr. Allen-Rhoades says. "In some cases, more tissue is required. Having patient specimens, integrated pathology and molecular testing in one location provides a significant advantage."
Expanding access to pediatric tumor genomic profiling
Pediatric tumor genomic testing used by Mayo Clinic Children's pediatric oncologists also is available to physicians nationwide through Mayo Clinic Laboratories. This access enables external clinicians to use the same precision diagnostics for pediatric cancer, regardless of whether a patient is receiving care at Mayo Clinic Children's.
Physicians may submit tissue samples for pathologic evaluation, genomic testing or both. If the pathologist's analysis indicates molecular testing, the pathologist an initiate the assay directly.
"Physicians may want the diagnostic capabilities we provide while continuing to manage care locally," Dr. Allen-Rhoades says. "It's important to emphasize that access to advanced molecular testing does not necessitate a transfer of care. Mayo Clinic Children's values collaborative partnership with referring providers."
For more information
Refer a patient to Mayo Clinic.