Faculty Collaboration Database

Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing. Cancer Res 2017 Oct 01;77(19):5419-5427

Date

08/16/2017

Pubmed ID

28807936

Pubmed Central ID

PMC5626633

DOI

10.1158/0008-5472.CAN-17-0885

Scopus ID

2-s2.0-85031426857 (requires institutional sign-in at Scopus site)   84 Citations

Abstract

Noninvasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers. The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%), or lung (20.7%). ctDNA obtained from most patients [N = 423 (63%)] displayed at least one alteration. The most frequent alterations seen, as characterized mutations or variants of unknown significance, occurred in TP53 (32.5% of patients), EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, 30.7% (TP53), 7.6% (EGFR), 12.2% (KRAS), and 7.7% (PIK3CA). We found that 32% of brain tumors had at least one ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations in a multivariable analysis (P = 0.019). Notably, 320/670 (48%) of patients displayed potentially actionable alterations, with 241 patients possible candidates for on-label or off-label treatment with an FDA-approved drug. Several illustrations of the clinical utility of the information obtained for improving treatment of specific patients is provided. Our findings demonstrate the feasibility and impact of genomic profiling of tumors by ctDNA NGS, greatly encouraging broader investigations of the application of this technology for precision medicine in cancer management. Cancer Res; 77(19); 5419-27. ©2017 AACR.

Author List

Schwaederle M, Chattopadhyay R, Kato S, Fanta PT, Banks KC, Choi IS, Piccioni DE, Ikeda S, Talasaz A, Lanman RB, Bazhenova L, 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

Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Child
Child, Preschool
DNA, Neoplasm
Female
Genomics
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Mutation
Neoplasms
Retrospective Studies
Young Adult