Molecular Analysis Of Solid Tumors

Trial Information

Molecular Analysis Of Solid Tumors

Each year approximately 2,200 children in the United States are diagnosed with
neuroblastoma, osteosarcoma, Ewing sarcoma family of tumors (ESFT), retinoblastoma and soft
tissue sarcomas. These aggressive pediatric solid tumors are developmental tumors that
initiate during periods of tissue growth and morphogenesis in the neural crest, bone and
soft tissues. The overall survival rate of these tumors in the advanced stage is less than
30%. Despite intensive efforts over the past three decades using multiple therapeutic
modalities including chemotherapy, surgery, radiation, autologous bone marrow transplant and
biological agents there has been modest improvement in the long-term survival of these
advanced stage pediatric solid tumors. A better understanding of the molecular, cellular and
genetic changes that occur in the developing tissues as tumors form could improve the
treatment of these devastating cancers. In particular, chemotherapeutic agents may be more
effectively targeted to key regulatory enzymes or proteins if the study had a better
understanding of the pathways that are disrupted as cells progress from preneoplastic
lesions to metastatic disease. The specific aim of this proposal is to identify the changes
in gene expression that occur in neuroblastoma, retinoblastoma, osteosarcoma, Ewing sarcoma
family of tumors [ESFT] and soft tissue sarcoma cells and to correlate these changes with
genetic and cellular changes in the tumor cells. [RNA] ribonucleic acid and genomic [DNA]
deoxyribonucleic acid will be isolated from neuroblastoma, retinoblastoma, osteosarcoma,
ESFT [Ewing sarcoma family of tumors] and soft tissue sarcomas (both primary and metastatic
lesions) following surgery or bone marrow aspiration of previously untreated patients.
Additional testing will be conducted on tumor samples at any point during or following
therapy in which a surgical specimen is obtained. When there is sufficient tumor sample
remaining after pathological analysis and banking, fresh primary tumor cells will be used to
prepare orthotopic xenografts and to establish models of each disease that recapitulate the
advanced forms of neuroblastoma, osteosarcoma, Ewing sarcoma family of tumors [ESFT],
retinoblastoma and soft tissue sarcomas. For a small group of these excess samples, this
study will perform fixation for electron microscopy and process the samples for [TEM]
transmission electron microscopy analysis. These studies will complement our active research
program characterizing the molecular, cellular and genetic features of genetically
engineered mouse models of each of these diseases. Biological samples from the cohort of
patients treated at St. Jude Children's Research Hospital will be complemented with samples
collected and processed by collaborating institutions around the world. Samples collected
from international collaborators will be used for analysis of [DNA] deoxyribonucleic acid
and [RNA] ribonucleic acid to complement the St. Jude Children's Research Hospital cohort.
Through this collaboration the study anticipates that they will be able to obtain enough
fresh tumor samples to improve their understanding of multistage tumorigenesis in pediatric
solid malignancies.