Theranostic profiling for actionable aberrations in advanced high risk osteosarcoma with aggressive biology reveals high molecular diversity: The human fingerprint hypothesis

Daniela Egas-Bejar, Pete M. Anderson, Rishi Agarwal, Fernando Corrales-Medina, Eswaran Devarajan, Winston W. Huh, Robert E. Brown, Vivek Subbiah

Research output: Contribution to journalArticle

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)167-179
Number of pages13
JournalOncoscience
Volume1
Issue number2
DOIs
StatePublished - 2014

Keywords

  • Biomarker
  • Bone tumors
  • CLIA
  • Next generation sequencing
  • Osteosarcoma
  • Sarcoma
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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