Skip to main content

Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer.

Publication ,  Journal Article
Strickler, JH; Loree, JM; Ahronian, LG; Parikh, AR; Niedzwiecki, D; Pereira, AAL; McKinney, M; Korn, WM; Atreya, CE; Banks, KC; Nagy, RJ ...
Published in: Cancer Discov
February 2018

"Liquid biopsy" approaches analyzing cell-free DNA (cfDNA) from the blood of patients with cancer are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cohorts of patients with cancer can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 patients with colorectal cancer. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based colorectal cancer sequencing compendia. Our analysis also identified a novel cluster of extracellular domain (ECD) mutations in EGFR, mediating resistance by blocking binding of anti-EGFR antibodies. Patients with EGFR ECD mutations displayed striking tumor heterogeneity, with 91% harboring multiple distinct resistance alterations (range, 1-13; median, 4). These results suggest that cfDNA profiling can effectively define the genomic landscape of cancer and yield important biological insights.Significance: This study provides one of the first examples of how large-scale genomic profiling of cfDNA from patients with colorectal cancer can detect genomic alterations at frequencies comparable to those observed by direct tumor sequencing. Sequencing of cfDNA also generated insights into tumor heterogeneity and therapeutic resistance and identified novel EGFR ectodomain mutations. Cancer Discov; 8(2); 164-73. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 127.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cancer Discov

DOI

EISSN

2159-8290

Publication Date

February 2018

Volume

8

Issue

2

Start / End Page

164 / 173

Location

United States

Related Subject Headings

  • Mutation
  • Humans
  • Genomics
  • Genome-Wide Association Study
  • ErbB Receptors
  • DNA, Neoplasm
  • Colorectal Neoplasms
  • Cohort Studies
  • Clonal Evolution
  • Cell-Free Nucleic Acids
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Strickler, J. H., Loree, J. M., Ahronian, L. G., Parikh, A. R., Niedzwiecki, D., Pereira, A. A. L., … Kopetz, S. (2018). Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer. Cancer Discov, 8(2), 164–173. https://doi.org/10.1158/2159-8290.CD-17-1009
Strickler, John H., Jonathan M. Loree, Leanne G. Ahronian, Aparna R. Parikh, Donna Niedzwiecki, Allan Andresson Lima Pereira, Matthew McKinney, et al. “Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer.Cancer Discov 8, no. 2 (February 2018): 164–73. https://doi.org/10.1158/2159-8290.CD-17-1009.
Strickler JH, Loree JM, Ahronian LG, Parikh AR, Niedzwiecki D, Pereira AAL, et al. Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer. Cancer Discov. 2018 Feb;8(2):164–73.
Strickler, John H., et al. “Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer.Cancer Discov, vol. 8, no. 2, Feb. 2018, pp. 164–73. Pubmed, doi:10.1158/2159-8290.CD-17-1009.
Strickler JH, Loree JM, Ahronian LG, Parikh AR, Niedzwiecki D, Pereira AAL, McKinney M, Korn WM, Atreya CE, Banks KC, Nagy RJ, Meric-Bernstam F, Lanman RB, Talasaz A, Tsigelny IF, Corcoran RB, Kopetz S. Genomic Landscape of Cell-Free DNA in Patients with Colorectal Cancer. Cancer Discov. 2018 Feb;8(2):164–173.

Published In

Cancer Discov

DOI

EISSN

2159-8290

Publication Date

February 2018

Volume

8

Issue

2

Start / End Page

164 / 173

Location

United States

Related Subject Headings

  • Mutation
  • Humans
  • Genomics
  • Genome-Wide Association Study
  • ErbB Receptors
  • DNA, Neoplasm
  • Colorectal Neoplasms
  • Cohort Studies
  • Clonal Evolution
  • Cell-Free Nucleic Acids