Tumor Fraction Guided Cell-Free DNA Profiling in Metastatic Cancer Patients

Description: Study Description from daGaP: "Cell-free DNA (cfDNA) profiling is increasingly used to guide cancer care, yet mutations are not always identified. The ability to detect somatic mutations in plasma depends on both assay sensitivity and the fraction of circulating DNA in plasma that is tumor-derived (i.e cfDNA tumor fraction). We hypothesized that cfDNA tumor fraction could inform the interpretation of negative cfDNA results and guide the choice of subsequent assays of greater genomic breadth or depth. Plasma samples collected from 118 metastatic cancer patients were analyzed with cf-IMPACT, a modified version of the FDA-authorized MSK-IMPACT tumor test that can detect genomic alterations in 410 cancer-associated genes. Shallow whole genome sequencing (sWGS) was also performed in the same samples to estimate cfDNA tumor fraction based on genome-wide copy number alterations using z-score statistics. The results show that cfDNA tumor fraction can inform the interpretation of negative cfDNA results and guide the selection of subsequent sequencing platforms that are most likely to identify clinically-relevant genomic alterations."

Whole genome sequencing of 118 tumor vs. matched-normal pairs.

Subject of Study

Homo sapiens

Subject(s)

Cell-Free Nucleic Acids

DNA Mutational Analysis

Access via dbGaP
BAM and SRA files of whole genome and exome sequencing
Accession #: phs002290.v1.p1

Access via BioProject
Additional information about overall initiative
Accession #: PRJNA679359
Access Restrictions: Application Required
Access Instructions: Full access to this dataset in dbGaP requires authorization through an Authorized Access Portal which can be requested for either 'data download' or 'view only'. Individual level data download requires a project request. With dbGaP DataBrowser approval, users may view the collection compilation of individual-level data from general research use. Upon approval data can be downloaded. The section "Publicly Available Data (Public ftp)" connects to a public download site containing "data dictionaries, variable summaries, documents and truncated analyses, whenever available."

A full list of and information about the SRA runs, BioSamples, and experiments is publicly viewable by going to the 'Molecular Datasets' tab and clicking on 'RunSelector' at the bottom of the page. This will take you to the NCBI SRA Run Selector platform, however view and download of the datasets themselves still requires authorization through dbGaP.
Associated Publications: Tsui DWY, Cheng ML, Shady M, et al. Tumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients. Genome Med. 2021;13(1):96. Published 2021 May 31.
Data Type: Genomic
Equipment Used: Illumina HiSeq 4000
High throughput gene sequencing system
Software Used: Burrows-Wheeler Aligner
BWA is a software package for mapping low-divergent sequences against a large reference genome, such as the human genome.

SRA Toolkit
The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.
Dataset Format(s): SRA, BAM
Data Tool(s): MSK-IMPACT

cf-IMPACT

WXS

WGS
Dataset Size: 115.9 GB

Data Catalog Record Updated: 2021-06-24