Faculty Collaboration Database

Hybrid Capture-Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Cancers of the Gastrointestinal Tract or Anus. Clin Cancer Res 2018 Apr 15;24(8):1881-1890

Date

01/25/2018

Pubmed ID

29363525

Pubmed Central ID

PMC6076990

DOI

10.1158/1078-0432.CCR-17-3103

Scopus ID

2-s2.0-85046659151 (requires institutional sign-in at Scopus site)   53 Citations

Abstract

Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal and anal cancers is increasingly used to inform treatment. In some cases, tissue biopsy can be prohibitive, and we sought to investigate whether analysis of blood-derived circulating tumor DNA (ctDNA) may provide a minimally invasive alternative.Experimental Design: Hybrid capture-based genomic profiling of 62 genes was performed on blood-based ctDNA from 417 patients with gastrointestinal carcinomas to assess the presence of genomic alterations (GA) and compare with matched tissue samples.Results: Evidence of ctDNA was detected in 344 of 417 samples (82%), and of these, ≥1 reportable GA was detected in 89% (306/344) of samples. Frequently altered genes were TP53 (72%), KRAS (35%), PIK3CA (14%), BRAF (8%), and EGFR (7%). In temporally matched ctDNA and tissue samples available from 25 patients, 86% of alterations detected in tissue were also detected in ctDNA, including 95% of short variants, but only 50% of amplifications. Conversely, 63% of alterations detected in ctDNA were also detected in matched tissue. Examples demonstrating clinical utility are presented.Conclusions: Genomic profiling of ctDNA detected potentially clinically relevant GAs in a significant subset of patients with gastrointestinal carcinomas. In these tumor types, most alterations detected in matched tissue were also detected in ctDNA, and with the exception of amplifications, ctDNA sequencing routinely detected additional alterations not found in matched tissue, consistent with tumor heterogeneity. These results suggest feasibility and utility of ctDNA testing in advanced gastrointestinal cancers as a complementary approach to tissue testing, and further investigation is warranted. Clin Cancer Res; 24(8); 1881-90. ©2018 AACR.

Author List

Schrock AB, Pavlick D, Klempner SJ, Chung JH, Forcier B, Welsh A, Young L, Leyland-Jones B, Bordoni R, Carvajal RD, Chao J, Kurzrock R, Sicklick JK, Ross JS, Stephens PJ, Devoe C, Braiteh F, Ali SM, Miller VA

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
Anus Neoplasms
Biomarkers, Tumor
Circulating Tumor DNA
Female
Follow-Up Studies
Gastrointestinal Neoplasms
Genomics
Humans
Male
Middle Aged
Mutation
Neoplasm Grading
Neoplasm Staging
Nucleic Acid Hybridization
Organ Specificity