Faculty Collaboration Database

Genome-wide Sequencing of Cell-free DNA Enables Detection of Copy-number Alterations in Patients with Cancer Where Tissue Biopsy is Not Feasible. Mol Cancer Ther 2021 Nov;20(11):2274-2279

Date

09/02/2021

Pubmed ID

34465593

Pubmed Central ID

PMC9398131

DOI

10.1158/1535-7163.MCT-20-1066

Scopus ID

2-s2.0-85119045480 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

When tissue biopsy is not medically prudent or tissue is insufficient for molecular testing, alternative methods are needed. Because cell-free DNA (cfDNA) has been shown to provide a representative surrogate for tumor tissue, we sought to evaluate its utility in this clinical scenario. cfDNA was isolated from the plasma of patients and assayed with low-coverage (∼0.3×), genome-wide sequencing. Copy-number alterations (CNA) were identified and characterized using analytic methods originally developed for noninvasive prenatal testing (NIPT) and quantified using the genomic instability number (GIN), a metric that reflects the quantity and magnitude of CNAs across the genome. The technical variability of the GIN was first evaluated in an independent cohort comprising genome-wide sequencing results from 27,754 women who consented to have their samples used for research and whose NIPT results yielded no detected CNAs to establish a detection threshold. Subsequently, cfDNA sequencing data from 96 patients with known cancers but for whom a tissue biopsy could not be obtained are presented. An elevated GIN was detected in 35% of patients and detection rates varied by tumor origin. Collectively, CNAs covered 96.6% of all autosomes. Survival was significantly reduced in patients with an elevated GIN relative to those without. Overall, these data provide a proof of concept for the use of low-coverage, genome-wide sequencing of cfDNA from patients with cancer to obtain relevant molecular information in instances where tissue is difficult to access. These data may ultimately serve as an informative complement to other molecular tests.

Author List

Jensen TJ, Goodman AM, Ellison CK, Holden KA, Kato S, Kim L, Daniels GA, Fitzgerald K, McCarthy E, Nakashe P, Mazloom AR, Almasri E, McLennan G, Grosu DS, Eisenberg M, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Cell-Free Nucleic Acids
DNA Copy Number Variations
Female
Humans
Male
Middle Aged
Neoplasms
Precision Medicine
Whole Genome Sequencing
Young Adult