Dataset Information

CSER: Incorporation of Genomic Sequencing into Pediatric Cancer Care

ABSTRACT:

This project includes data derived from subjects enrolled in the BASIC3 (Baylor College of Medicine Advancing Sequencing in Childhood Cancer Care) study. BASIC3 is a National Genome Human Research Institute (NHGRI) and National Cancer Institute-funded Clinical Sequencing Exploratory Research (CSER) consortium project that focused on prospective implementation of clinical whole exome sequencing in the pediatric oncology clinic. The primary study objective were to integrate information from CLIA-certified germline and tumor exome sequencing into the care of newly diagnosed solid tumor patients at Texas Children's Cancer Center, and to perform parallel evaluation of the impact of tumor and germline exomes on families and physicians.

Blood and frozen tumor (if available) samples were collected from children undergoing surgery or biopsy of newly diagnosed solid tumors and subjected to exome sequencing in a CLIA-certified laboratory. Germline and tumor (if applicable) exome sequencing reports were generated and submitted into the electronic health record and returned to each patient/family by their primary oncologist.

In addition to the clinical exome sequencing, specific (optional) consent was requested for research sequencing studies. If this consent was obtained then research studies of some of the children and parents participating in the BASIC3 study (including tumor transcriptome and whole genome sequencing of blood and/or tumor) are performed.

The Clinical Sequencing Exploratory Research Consortium Cohort is utilized in the following dbGaP sub-study. To view molecular data, and derived variables collected in this sub-study, please click on the following sub-studies below or in the "Sub-study" box located on the right hand side of this top-level study page phs001383 Clinical Sequencing Exploratory Research Consortium Cohort.

phs001026 BASIC3
phs001878 GMKF BASIC3

PROVIDER: phs001683 | dbGaP |

REPOSITORIES: dbGaP

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	GapExchange_phs001683.v1.p1.xml	Xml
	dbGaPEx2.1.5.xsd	Other
	Study_Report.phs001683.CSER_PediatricCancerCare.v1.p1.MULTI.pdf	Pdf
	manifest_phs001683.CSER_PediatricCancerCare.v1.p1.c1.GRU-PUB.pdf	Pdf
	datadict_v2.xsl	Other

Items per page:

1 - 5 of 34

Similar Datasets

Project description:Whole genome sequencing (WGS) and whole exome sequencing (WES) services are currently available to and being utilized by physicians and their patients in both research and clinical settings, and recently to anyone in the general public via direct-to-consumer companies. But the widespread availability and use of WGS and WES in the practice of clinical medicine is imminent. In the very near future, sequencing of individual genomes will be inexpensive and ubiquitous, and patients will be looking to the medical establishment for interpretations, insight and advice to improve their health. Developing standards and procedures for the use of WGS information in clinical medicine is an urgent need, but there are numerous obstacles related to integrity and storage of WGS data, interpretation and responsible clinical integration. The MedSeq Project is an exploratory trial of WGS in clinical medicine. At the conclusion of this study, we will have helped create innovative protocols and novel outcome measures that can be applied safely in future large-scale multi-site randomized clinical trials with larger numbers of physicians from broad specialties and with more economically and ethnically diverse patients. Together with our colleagues from across the nation through the U01 consortium formed as a result of this funding from the NIH, we will have invented a process of implementation and evaluation whereby the fruits of the Human Genome Project can be applied for the first time to the daily practice of medicine for the betterment of human health. The objectives of the MedSeq Project are to: <ol> <li>Recruit, consent and enroll 2 study groups:</li> <ol type="a"> <li>10 primary care physicians and 100 of their healthy middle-aged patients </li> <li>10 cardiologists and 100 of their patients with cardiomyopathy.</li> </ol> <li>Randomize each study group to receive standard of care versus standard of care plus WGS.</li> <li>Monitor the entire protocol for subject safety.</li> <li>Only half the enrolled patients were selected for sequencing. Fifty subjects were selected from the primary care cohort and fifty were selected from the cardiomyopathy cohort. Whole genome sequencing was performed at 30x coverage in Illumina's CLIA-certified laboratory on these 100 individuals.</li> <li>Generate and optimize an algorithm for interpreting WGS data covering the spectrum of human genetic variation, in terms of both previously reported and novel variants likely to influence the health of patients.</li> <li>Create patient reports and provide an interface for communicating clinically relevant genomic information to practicing physicians.</li> <li>Describe physicians' and patients' attitudes toward, and preferences for, the disclosure of WGS results at the start of the study.</li> <li>Evaluate physicians' experiences with receiving and interpreting patients' genetic test results and how they communicate these results to their patients.</li> <li>Explore how patients respond to and use WGS results by administering validated scales of psychological impact, personal utility, and behavioral responses, as well as economic and health outcomes.</li> </ol> Although we do not have a large enough sample size for statistical comparisons of outcomes, we will conduct exploratory comparisons: Exploratory Hypotheses: <ul> <li>Patients who receive WGS results will show equivalent levels of distress compared to patients who receive family history only.</li> <li>Patients with higher genetic literacy and better understanding will report greater satisfaction and less decisional regret.</li> <li>Patients who receive WGS will (a) be more likely to change health behaviors and (b) utilize more health care resources than those who do not receive WGS.</li> </ul>

Project description:Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer with high intra-tumoral heterogeneity, frequently resistant to treatment and no known targeted therapy available to improve patient outcomes. It has been hypothesized that the genomic architecture of a TNBC tumour evolves over time, both before, and during therapy, leading to therapy resistance and a high propensity to relapse. Whether this is an inherent property of the tumour or acquired over time is not well characterized. Despite this important clinical implication, limited studies have been carried out to unravel temporal evolution of TNBC over time. Herein, we report an OMICS based analysis of three TNBC patients who were longitudinally sampled during their treatment at different times of relapse. We recruited three TNBC patients at the time of their first relapse who were then followed-up through the course of their treatment. We obtained retrospective samples (tumour samples) from patient tumours at diagnosis (before neo-adjuvant chemotherapy - NACT) at surgery (post NACT) and prospectively sampled them at each subsequent relapse (tumour, blood plasma, and buffy coat) as determined by RECIST criteria. Tumor and buffy coat DNA were subjected to whole exome sequencing (WES) at 200x, and SNP arrays for copy number variation (CNV) analysis. RNA from tumour samples at relapse was subjected to whole transcriptome sequencing. Pathogenic germline BRCA1 variants identified in WES were validated using Sanger sequencing. 1084 somatic mutations identified in whole exome sequencing of all tumour tissues (n=13) from three patients, were subjected to a custom amplicon ultra-deep sequencing assay at 30,000X in their germline DNA (n=3), tumour DNA (n=10), and cfDNA from plasma samples at relapse (n=8). Copy number corrected allele frequencies, tumour ploidy, tumour purity, and ultra-deep sequencing assay derived variant allele frequencies were used to infer clonal and phylogenetic architecture of each patient as it evolved under selective pressure of therapy over time. Clonality analysis incorporating allele fractions from ultra-deep sequencing identified clones comprising of mutations that are present throughout the course of therapy which we term as founding clones and stem mutations respectively. Such founding clones comprising of stem mutations in all 3 patients were present throughout the course of treatment, irrespective of change in treatment modalities. These stem clones included well characterized cancer related genes like PDGFRB & ARID2 (Patient 02), TP53, BRAF & CSF3R (Patient 04) and ESR1, APC, EZH2 & TP53 (Patient 07). Such branching evolution is seen in all three patients wherein the dominant clone (stem clone) acquires additional mutations to form sub-clones, while persisting over time. These sub-clones may be chemo and radio resistant, while also providing for organ specific metastatic potential. Allele fractions of expressed variants inferred from RNA-Seq data co-related with allele fractions from WES data indicating that all somatic.

Dataset Information

CSER: Incorporation of Genomic Sequencing into Pediatric Cancer Care

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets