Theresa Beech’s Research

While caring for Daniel, Theresa started receiving questions from other osteosarcoma parents regarding the tumor genetics. One parent, led to another, and another and another. And through a fortuitous series of circumstances, Theresa was provided with a de-identified osteosarcoma tumor genetics data set of 63 pediatric tumors from Foundation One. With this data along with the data provided by parents, Theresa carried out a statistical and pattern detection analysis of osteosarcoma genetics.

The results of this analysis include:

  • the identification of the driving gene behind osteosarcoma (TP53)
  • a hypothesis for how osteosarcoma develops and why it responds poorly to treatment
  • the high prevalence of epigenetic regulation within the tumors and the main transcriptional factors responsible for this regulation
  • the relationships between various transcriptional factors, oncogenes, and tumor suppressor genes
  • a clear signal of Alternative Lengthening of Telomeres (ALT+)
  • a regression analysis which identified seven statistically significant and biologically relevant genetic phenotypes of osteosarcoma.  

As genetic data from parents and patients continued to pour in, Theresa provided genetic analysis to parents and patients, and started receiving medical history data to go with the genetic data. With this data, Theresa has detected trends between tumor genetics and medical outcome, including the genetic markers for the very high risk kids (MYC amplification, ATRX mutation/deletion), the kids who relapse many times but ultimately may become long-term NED, the kids who have the best response to chemotherapy (RB1 deleted/mutated), the kids who statistically should be dead due to very heavy metastatic tumor burden and poor response to chemo but are long-term survivors, and the kids who never make it to NED. Some patients have provided multiple snapshots of tumor genetic data, and with this information, it is possible to start to see how tumors evolve genetically in response to therapy.

In May, 2017, with over 110 tumors with genetic information, the Patient/Parent Osteosarcoma Genome-Wide Registry (POWR) received IRB approval for data capture and analysis from Hummingbird IRB, Cambridge, MA.

Theresa has discussed and provided the results of her analysis to osteosarcoma doctors, researchers, parents and patients around the US. She presented her research as part of the Keynote Speech at the recent Osteosarcoma FACTOR 2017 conference in Miami, FL in February, 2017. She is part of the Working Group as a patient advocate for a Phase 2 Basket Trial for Relapsed/Refractory Osteosarcoma which will combine chemotherapy with a targeted therapy based upon a patient’s tumor genetics. The POWR data and analysis form a key part of the scientific rationale of the trial. Doctors from MD Anderson, Dana Farber, Moffitt, CHLA, UCSF are current members of the Working Group including Drs Richard Gorlick and Katherine Janeway, the COG Bone Sarcoma Committee Chair and Vice-Chair respectively. She is currently raising funds for this potentially ground-breaking trial to go forward.

Current osteosarcoma outcomes are poor. Fewer than half will survive five years and almost all who do survive are handicapped. This situation has not changed in 30 years. No child should ever suffer as Daniel did, and no sister and mother should be left behind to grieve the death of a 13 year old brother and child. Daniel never gave up. He was brave, beautiful and beloved. #ItIsNotOk