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Theranostic Profiling for Actionable Aberrations in Advanced High Risk Osteosarcoma with Aggressive Biology Reveals
Daniela Egas-Bejar1, Pete M Anderson2, Rishi Agarwal3
1Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Abstract:
The survival of patients with advanced osteosarcoma is poor with limited therapeutic options. There is an urgent need for new targeted therapies based on biomarkers. Recently, theranostic molecular profiling services for cancer patients by CLIA-certified commercial companies as well as in-house profiling in academic medical centers have expanded exponentially. We evaluated molecular profiles of patients with advanced osteosarcoma whose tumor tissue had been analyzed by one of the following methods: 1. 182-gene next-generation exome sequencing (Foundation Medicine, Boston, MA), 2. Immunohistochemistry (IHC)/PCR-based panel (CARIS Target Now, Irving, Tx), 3.Comparative genome hybridization (Oncopath, San Antonio, TX). 4. Single-gene PCR assays, PTEN IHC (MDACC CLIA), 5. UT Houston morphoproteomics (Houston, TX). The most common actionable aberrations occur in the PI3K/PTEN/mTOR pathway. No patterns in genomic alterations beyond the above are readily identifiable, and suggest both high molecular diversity in osteosarcoma and the need for more analyses to define distinct subgroups of osteosarcoma defined by genomic alterations. Based on our preliminary observations we hypothesize that the biology of aggressive and the metastatic phenotype osteosarcoma at the molecular level is similar to human fingerprints, in that no two tumors are identical. Further large scale analyses of osteosarcoma samples are warranted to test this hypothesis.
Insights
Advanced osteosarcoma patients have poor survival and limited options. Molecular profiling reveals common aberrations in the PI3K/PTEN/mTOR pathway, highlighting the need for targeted therapies and further research into tumor diversity.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Advanced osteosarcoma presents a significant clinical challenge with poor patient survival and limited therapeutic strategies.
- The increasing availability of molecular profiling services necessitates an understanding of actionable genomic alterations in osteosarcoma.
- Biomarker-driven targeted therapies are crucial for improving outcomes in patients with advanced osteosarcoma.
Purpose of the Study:
- To evaluate the molecular profiles of advanced osteosarcoma tumors.
- To identify common actionable genomic aberrations and pathways implicated in osteosarcoma.
- To explore the molecular diversity of osteosarcoma and its implications for personalized medicine.
Main Methods:
- Analysis of tumor tissue from advanced osteosarcoma patients using diverse molecular profiling techniques.
- Methods included 182-gene next-generation exome sequencing, immunohistochemistry/PCR-based panels, comparative genome hybridization, single-gene PCR assays, and morphoproteomics.
- Specific assays included PTEN immunohistochemistry (IHC) and various commercial and academic profiling services.
Main Results:
- The PI3K/PTEN/mTOR pathway was identified as the most frequent site of actionable aberrations in advanced osteosarcoma.
- No distinct patterns in genomic alterations were readily identifiable beyond the PI3K/PTEN/mTOR pathway.
- Observations suggest significant molecular heterogeneity among osteosarcoma tumors.
Conclusions:
- Actionable aberrations in the PI3K/PTEN/mTOR pathway represent a potential therapeutic target in advanced osteosarcoma.
- The high molecular diversity observed in osteosarcoma underscores the need for extensive analyses to define distinct molecular subgroups.
- Further large-scale genomic analyses are warranted to test the hypothesis that each osteosarcoma tumor has a unique molecular fingerprint, guiding the development of novel targeted therapies.
