Patient/Parent Osteosarcoma Genome-Wide Registry (POWR) Provides the Sarcoma Community with an Underutilized Resource for Genomic and Medical History Data

Objective: Patient derived data is an underutilized resource for obtaining data on poor prognosis sarcomas such as relapsed/refractory osteosarcoma. Communicating primarily on-line with patients/parents, the osteosarcoma community  created a Patient/Parent Osteosarcoma Genome-Wide Registry (POWR) containing genomic and medical history information on >110 tumors. We will share insights from the first-ever patient/parent derived osteosarcoma genome-wide registry.

Methods: Genomic reports (primarily Foundation One or MSKCC IMPACT) and medical history information of 50 tumors were provided by patients/parents. Genetic sequencing data on 63 pediatric tumors was a downloaded from the pediatric data portal of Foundation One. IRB approval for data capture and analysis was granted by Hummingbird IRB, Cambridge, MA. Genomic reports identified Genomic Alterations (GA: base substitutions, indels, copy number alterations, fusions/rearrangements) and Variants of Unknown Significance (VUS). Medical history data includes: disease presentation; % necrosis; surgeries; time to relapse; number/location of relapses; treatments received; time to death.

Results: Mean number of GA (with VUS) is 13.8, range 1 – 46; mean age is 16, range 5 – 52; sex ratio is 63%/37% male/female. Table 1 shows the % occurrence of genes with GA & VUS. Co-amplification loci occur at 8q21-8q24 (MYC, RAD21, RUNX1T1) and 17p11-17p12 (C17orf39, NCOR1, FLCN). ATRX and MYC are mutually exclusive. Alternative Lengthening of Telomeres appears in 40-50% of tumors. Regression analysis of top 50 genes (GA only) yields 7 genomic sub-types (see image 1).

MYC amplified tumors have a trend to poor outcomes.  Of 13 MYC tumors with medical history data, 10 are dead or on hospice, 2 have at least bilateral lung metastases, and 1 is NED. 5/13 were never NED, 6/13 progressed on chemo. Mean time to death is 18 months, and mean time to initial relapse is 4 months (range 0-18 months). Initial disease presentation is not significant, nor is % tumor necrosis (mean 54%, range 5-95%). Overall mean % tumor necrosis is 51%, range 0-97%. RB1 tumors have a significantly higher mean % tumor necrosis (86%) compared to others (43%).

Conclusions: Statistical analysis of patient-derived relapsed/refractory osteosarcoma tumor data yields new insights into the genomics, as well as identifying a potential biomarker for poor outcome patients. POWR provides a model of patient/parent provided genomic and medical history data which can be a resource for the sarcoma community.



Theresa Beech

Colleen Pearson

Peter Anderson