Next Generation Sequencing of Normal Tissues Prospectively in Pediatric Oncology Patients

PRIMARY OBJECTIVES:

• To use clinical genomic sequencing to define the prevalence and spectrum of germline mutations in cancer predisposition genes in children with cancer.
• For those identified with germline mutations, to correlate germline genomic information with clinical presentation, tumor genomic findings, treatment response, and outcome.

OTHER PRESPECIFIED OBJECTIVES:

• To generate and analyze data describing patient/parent perceptions of genomic investigations and research at various time points throughout the study.
• To generate and analyze data surrounding the return of genomic sequencing results, examine patient/parent understanding of these results and assess the impact of results on patients and families.
• To determine the feasibility and reliability of performing WES and RNA sequencing on derivatives from formalin-fixed, paraffin-embedded (FFPE) tumor samples alongside the analysis of matched frozen tumor and germline samples.

For participants who give consent, a normal tissue sample will be obtained and used for WGS, WES and RNA sequence analysis. A defined list of 150 genes will be analyzed for reporting using the normal tissue. Once the results of these analyses are available, they will be disclosed to physicians, patients and parents. Mixed measures approaches will be used to assess understanding, acceptance and impact of genomic results on patients and parents. During the course of the study, the investigators anticipate the list of genes to be reported using normal tissue to change due to advances in the literature or other evidence linking additional genes to tumor formation and cancer risk, and new lists may be defined.

To assess provider, patient and family understanding and describe the impacts of genomic testing and return of results, this study will also incorporate administration of surveys and semi-structured interviews. Surveys and interviews are optional, but will be offered to all primary SJCRH providers, as well as all eligible participants and parents, regardless of whether or not they consent to pursue the genomic testing.

A sample of blood or a skin biopsy will be obtained as a source of germline DNA. This sample is necessary as it is the comparator against which tumor samples are evaluated. Skin biopsies may be done on patients who have a diagnosis where peripheral blood is likely to be contaminated by tumor cells.

Inclusion criteria

• St. Jude patients prospectively identified at the time of study activation with a diagnosed solid or liquid tumor (benign or malignant).
• Adequate tissue must be available (e.g. sufficient germline and/or tumor tissue, from which >1 µg DNA and >0.1 µg RNA must be isolated). Patients who have no tumor tissue available may enroll using only germline sample.

Exclusion criteria

• Past history of hematopoietic stem cell transplantation (or other condition that would result in hematopoietic cell DNA failing to match host tissue DNA).
• Tumor or germline tissue not meeting the criteria listed above.
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
• Participants who are unable to read, write or converse fluently in English or Spanish will be excluded from Prespecified Objectives 3 and 4.