Next Generation Sequencing of Normal Tissues Prospectively in Pediatric Oncology Patients

Summary

The development of next generation sequencing (NGS) techniques, including whole genome (WGS), exome (WES) and RNA sequencing has revolutionized the ability of investigators to query the molecular mechanisms underlying tumor formation. Through the Pediatric Cancer Genome Project (PCGP), investigators at St. Jude Children's Research Hospital (SJCRH) have successfully used NGS approaches to evaluate more than 1,000 pediatric cancers ranging from hematologic malignancies to central nervous system (CNS) and non-CNS solid tumors. From these and related studies, it has become clear that genomic approaches can accurately classify tumors into distinct pathologic and prognostic subtypes and detect alterations in cellular pathways that may serve as novel therapeutic targets. Collectively, these studies suggest that by characterizing the genomic make-up of individual tumors, investigators will be able to develop personalized and potentially more effective cancer treatments and/or preventive measures.

This protocol was initially enacted to usher NGS approaches into routine clinical care. During the initial phase of the G4K protocol, 310 participants were recruited and enrolled onto the study. Tumor and/or germline sequencing was completed on all 310 patients, with 253 somatic reports generated (representing 96% of the 263 participants for whom tumor tissue was available and analyzed) and 301 germline reports generated (100% of the 301 participants who agreed to the receipt of germline results). Analyses of the study data are ongoing with plans to prepare initial manuscripts within the next several months. Due to the successful initial execution of the G4K protocol, clinical genomic sequencing of tumor and germline samples is now offered as part of standard clinical care for pediatric oncology patients at St. Jude.

The G4K protocol has now been revised. With the revision, the study team will record, store and analyze germline and tumor genomic information. Through the collection of these data, we will examine how germline mutations in 150 cancer predisposition genes influence clinical presentation, tumor histology, tumor genomic findings, response to therapy and long-term outcomes. The overall goals of this research are to further define the prevalence, spectrum and heritability of germline variants in these genes and to decipher how germline mutations influence the phenotypes of an expanding array of cancer predisposition syndromes. These studies allow us to provide more accurate genetic counseling and management strategies to future children harboring mutations in these genes.

This remains a non-therapeutic study. Investigators anticipate a sample size of approximately 2500 patients who will be recruited over the next 7 years.

Conditions

• Solid, Liquid, Central Nervous System Tumors

Interventions

OTHER

Study Introduction Visit

Within 5±3 weeks following arrival at SJCRH, or at the participant/family's convenience, participants will meet with a genetic counselor and clinician, provide information for a family pedigree, undergo a physical and discuss germline testing options. Study introduction materials will be provided. Families interested in the G4K study will be referred to the study nurse or other G4K member and an Informed consent visit will be scheduled.

OTHER

Informed Consent Visit

Within 1±3 weeks following the Study Introduction Visit, or at the participant/family's convenience, the research nurse or other study team member will consent the family and collect demographic and medical information. Participants will complete assessment questionnaires.

OTHER

Informed Consent Follow-Up Visit

At or after enrollment but before the release of the gerline results, or at the participant/family's convenience, a subset of participants (30-40) will participate in semi-structured interviews.

OTHER

Return of Results Conversation

Participants will complete the assessment questionnaires.

OTHER

Return of Results Follow-Up Visits

Return of Results Follow-Up Visits will be conducted twice: the first within 8±4 weeks of the Return of Results Conversation, or at the participant/family's convenience, and the second within 28 ± 4 weeks of the Return of Results Conversation or at the participant/family's convenience. At each visit, participants will complete assessment questionnaires. Semi-structured interviews with parents and adolescents will be conducted.

PROCEDURE

Blood Sample

For patients who have not previously provided a blood sample, a sample of blood will be obtained as a source of germline DNA.

PROCEDURE

Skin Biopsy

After consent, for participants with a diagnosis where peripheral blood is likely to be contaminated by tumor cells, skin biopsies may be done as a source of germline DNA.

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Kim E. Nichols, MD · St. Jude Children's Research Hospital

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-08-28

Primary Completion

2033-12-31

Completion

2038-12-31

Countries

• United States

Study Locations