Clinical Targeted Next-Generation Panel Sequencing Reveals MYC Amplification Is a Poor Prognostic Factor in...

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Current osteosarcoma risk stratification, unchanged for decades, lacks genomic insights and has not driven treatment advances.
• Existing methods rely on metastatic status and chemotherapy response, failing to incorporate crucial molecular information.
• There is a critical need for advanced risk stratification tools in osteosarcoma.

Purpose of the Study:

• To investigate the genomic features of advanced osteosarcoma.
• To determine if genomic alterations can be utilized for improved risk stratification.
• To identify specific genomic events correlated with patient outcomes.

Main Methods:

• Targeted next-generation sequencing (OncoPanel and MSK-IMPACT) of 92 high-grade osteosarcoma patients (primary cohort) and 86 localized osteosarcoma patients (validation cohort).
• Assessment of the genomic landscape, including frequently altered genes and mutational signatures.
• Evaluation of the correlation between recurrent genomic events and overall survival (OS).

Main Results:

• Three-year OS was 65% in the primary cohort; metastatic disease at diagnosis was linked to poorer OS (P=.04).
• Key altered genes included TP53, RB1, MYC, CCNE1, CCND3, CDKN2A/B, and ATRX.
• MYC amplification correlated with worse 3-year OS in both primary (P=.015) and validation (P=.012) cohorts.

Conclusions:

• Genomic alterations in osteosarcoma are identifiable using targeted next-generation sequencing.
• MYC amplification is a significant genomic event associated with poorer outcomes in osteosarcoma.
• Genomic profiling offers a promising approach for refining osteosarcoma risk stratification and potentially guiding treatment decisions.