title: Theranostic Profiling for Actionable Aberrations in Advanced High Risk Osteosarcoma with Aggressive Biology Reveals High Molecular Diversity: The Human Fingerprint Hypothesis.
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,PTENIHC (MDACC CLIA), 5. UT Houston morphoproteomics (Houston, TX). The most common actionable aberrations occur in thePI3K/PTEN/mTORpathway. 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.
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
authors.forename: Daniela
authors.initials: D
authors.lastname: Egas-Bejar
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 ; Pediatric Hematology/ Oncology/ BMT, Levine Children's Hospital/ Levine Cancer Institute, 1000 Blythe Boulevard, Charlotte, NC 28203.
authors.forename: Pete M
authors.initials: PM
authors.lastname: Anderson
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
authors.forename: Rishi
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
authors.forename: Fernando
authors.initials: F
authors.lastname: Corrales-Medina
authors.affiliation: Department of Orthopedic Oncology- Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
authors.forename: Eswaran
authors.initials: E
authors.lastname: Devarajan
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
authors.forename: Winston W
authors.initials: WW
authors.lastname: Huh
authors.affiliation: Department of Pathology, UT Health-Department of Pathology and Laboratory medicine, 6431 Fannin Street, Houston, Texas 77030 Houston, TX 77030.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
keywords: Bone tumors; CLIA; Next generation sequencing; Osteosarcoma; Sarcoma; Targeted therapy; biomarker