Comprehensive Omics Analysis of Pediatric Solid Tumors and Establishment of a Repository for Related Biological Studies
-Laboratory-based investigations have contributed to an improved understanding of the
biology of cancer and to the development of new therapies for pediatric malignancies.
- Systematic Molecular, Genomic, Proteomic, Metabolomic ( Omic ) and other profiling for
consenting patients enrolled at the Pediatric Oncology Branch, Children's National
Medical Center (CNMC), Carolinas Medical Center/Levine Children's Hospital, and
- Establish a sample acquisition protocol for the collection and banking of pediatric
solid tumors and paired normal tissue to support research conducted by the
collaborative studies at the NIH, Children's National Medical Center (CNMC), Carolinas
Medical Center/Levine Children's Hospital, and other extramural institutions.
- Investigate the growth factor and cellular profile of different pediatric and adult
malignancies and correlate this with disease course by measuring circulating levels of
growth factors, microvesicles and bone marrow-derived cells including hematopoietic
progenitor cells (HPCs), endothelial progenitor cells (EPCs), mesenchymal progenitor
cells (MPCs) and matrix metalloproteases (MMPs) in the blood and urine of pediatric and
adult patients without malignancy, as well as patients with pediatric and adult
malignancies, and determining if these levels predict development of metastasis, or
change during treatment, such as when undergoing surgery, chemotherapy and other
treatments such as immunotherapy.
- Identify caregiver attitudes toward the use of next generation sequencing (NGS) at the
NIH for diagnosing and managing pediatric cancer and the return of NGS genetic test
incidental findings to caregivers.
- Evaluate the anticipated short- and long-term impact of returning NGS genetic test results
for cancer and incidental findings on quality of life and related bioethical outcomes among
NIH patients, caregivers, and the family system.
- Subjects with a diagnosis of any tumor or malignancy regardless of age, or without
malignancy undergoing surgery, other treatment or normal well visit.
- Suspicion of a familial premalignant condition.
- Biological relatives of a subject with a pediatric tumor or malignancy or with
suspected familial cancer syndrome.
- Biological relatives of a subject with an adult tumor or malignancy or with suspected
familial cancer syndrome.
- Blood and/or tissue specimens that have been previously collected and are available for
study or that can be collected with minimal additional risk to the subject during
sampling required for routine patient care.
- This study will allow for the collection of specimens for a Tissue Repository, and for
designated sample investigations including systematic molecular, genomic and proteomic
(Omic) profiling, and growth factor and cellular profile investigations.
- Specimens will be collected and stored at the Advanced Technology Center, Gaithersburg,
- Linked clinical and demographic data will be stored in the HIPAA compliant, secure
web-based database (Labmatrix).
- Testing activities may include:
- DNA, RNA and protein will be extracted from a section of tumor samples, the
remainder will be stored.
- Germ line DNA and RNA will be extracted from lymphocytes or other normal
- Germ line DNA will be extracted from lymphocytes or other normal uninvolved tissue
of the biological relatives of the subject.
- Xenografts and cell lines will be established from tumor samples
- Blood and/or Bone Marrow will be sent to Coriell Institute for Medical Research
for the establishment of EBV transformed cell lines.
- Tumor samples sent to Molecular Response for the establishment of Xenografts and
single cell suspension of tumor for drug testing
- Omics (Genomics and Proteomic) studies will be performed
- Growth factor and cellular profile investigations of bone marrow-derived cell
populations to include quantification of hematopietic progenitor cells (HPCs),
endothelial progenitor cells (EPCs), and mesenchymal progenitor cells (MPCs),
levels of matrix metalloprotease 2 and 9 (MMP2) and (MMP9), gene expression,
growth factor and microvesicle analysis and bone marrow analysis of progenitor
cells in blood and tissue.
- Establishing an oversight committee to oversee the receipt and the distribution of
unlinked tissues to other investigators.
- Qualitative methodologies will be used to ascertain knowledge, attitudes, beliefs, and
behaviors in 25-35 parents/caregivers at NIH concerning the anticipated use of NGS for
diagnosing and directing therapy for pediatric cancer and how incidental findings might
- Expected accrual 50-100 patients per year per center equaling approximately 150
enrolled per year. Total protocol accrual goal 2,000 patients and 4000 biologic relatives,
and up to 35 caregivers, for a total of 6035 participants.
Time Perspective: Retrospective
Javed Khan, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Childrens National Medical Center||Washington, District of Columbia|