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

TitleClinical Targeted Next-Generation Panel Sequencing Reveals MYC Amplification Is a Poor Prognostic Factor in Osteosarcoma.
Publication TypeJournal Article
Year of Publication2023
AuthorsMarinoff AE, Spurr LF, Fong C, Li YY, Forrest SJ, Ward A, Doan D, Corson L, Mauguen A, Pinto N, Maese L, Colace S, Macy ME, Kim AR, Sabnis AJ, Applebaum MA, Laetsch TW, Glade-Bender J, Weiser DA, Anderson M, Crompton BD, Meyers P, Zehir A, MacConaill L, Lindeman N, Nowak JA, Ladanyi M, Church AJ, Cherniack AD, Shukla N, Janeway KA
JournalJCO Precis Oncol
Date Published2023 Mar
KeywordsBone Neoplasms, Gene Amplification, High-Throughput Nucleotide Sequencing, Humans, Mutation, Osteosarcoma, Prognosis

PURPOSE: Osteosarcoma risk stratification, on the basis of the presence of metastatic disease at diagnosis and histologic response to chemotherapy, has remained unchanged for four decades, does not include genomic features, and has not facilitated treatment advances. We report on the genomic features of advanced osteosarcoma and provide evidence that genomic alterations can be used for risk stratification.

MATERIALS AND METHODS: In a primary analytic patient cohort, 113 tumor and 69 normal samples from 92 patients with high-grade osteosarcoma were sequenced with OncoPanel, a targeted next-generation sequencing assay. In this primary cohort, we assessed the genomic landscape of advanced disease and evaluated the correlation between recurrent genomic events and outcome. We assessed whether prognostic associations identified in the primary cohort were maintained in a validation cohort of 86 patients with localized osteosarcoma tested with MSK-IMPACT.

RESULTS: In the primary cohort, 3-year overall survival (OS) was 65%. Metastatic disease, present in 33% of patients at diagnosis, was associated with poor OS (P = .04). The most frequently altered genes in the primary cohort were TP53, RB1, MYC, CCNE1, CCND3, CDKN2A/B, and ATRX. Mutational signature 3 was present in 28% of samples. MYC amplification was associated with a worse 3-year OS in both the primary cohort (P = .015) and the validation cohort (P = .012).

CONCLUSION: The most frequently occurring genomic events in advanced osteosarcoma were similar to those described in prior reports. MYC amplification, detected with clinical targeted next-generation sequencing panel tests, is associated with poorer outcomes in two independent cohorts.

Alternate JournalJCO Precis Oncol
PubMed ID36996377
PubMed Central IDPMC10531050
Grant ListK08 CA218691 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
T32 CA128583 / CA / NCI NIH HHS / United States
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