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, soft tissue sarcomas,
adrenocortical tumors and liver malignancies. 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.

Inclusion Criteria:

- Must have a suspected or known diagnosis of neuroblastoma, osteosarcoma, Ewing sarcoma
family of tumor or soft tissue sarcoma based on the initial diagnostic workup and
evidence of gross disease amenable to excision. Specimens may be collected at some or
all of the following time points: initial biopsy, bone marrow aspiration procedures,
tumor resection, and at time of possible relapse.

- Patients with a diagnosis of retinoblastoma based on initial diagnostic workup and who
require enucleation may be enrolled if there is no active therapeutic or biologic
protocol for retinoblastoma.

- The patient or his/her legal guardian, as appropriate, must provide written informed
consent within 30 days of the removal of the first collection of tissue/bone
marrow/blood sample for this protocol.

- The patient is being seen at St. Jude Children's Research Hospital or at a
collaborating institution.

- Patients must be less than or equal to 25 years old at the time of enrollment.

Exclusion Criteria:

- Patient is known to be Hepatitis B, Hepatitis C and/or HIV positive.