Skip to main content
eScholarship
Open Access Publications from the University of California

Hybrid Capture-Based Genomic Profiling of Circulating Tumor DNA from Patients with Advanced Non-Small Cell Lung Cancer.

  • Author(s): Schrock, Alexa B
  • Welsh, Allison
  • Chung, Jon H
  • Pavlick, Dean
  • Bernicker, Eric H
  • Creelan, Benjamin C
  • Forcier, Brady
  • Ross, Jeffrey S
  • Stephens, Philip J
  • Ali, Siraj M
  • Dagogo-Jack, Ibiayi
  • Shaw, Alice T
  • Li, Tianhong
  • Ou, Sai-Hong Ignatius
  • Miller, Vincent A
  • et al.

Published Web Location

https://pdf.sciencedirectassets.com/313381/1-s2.0-S1556086418X00173/1-s2.0-S1556086418332052/main.pdf?X-Amz-Date=20190822T040532Z&X-Amz-Algorithm=AWS4-HMAC-SHA256&X-Amz-Signature=9bf6f842936b5b3b7edc24380ca64d2d3b89e0e4dccc157930709ee1b7263d43&X-Amz-Credential=ASIAQ3PHCVTYQ235ZUY3%2F20190822%2Fus-east-1%2Fs3%2Faws4_request&type=client&tid=prr-9c8c2ee8-d7cb-4bfc-ba08-f23b1fb5363c&sid=a6b4cbba2a5b3841743a49b38c6003db0db8gxrqa&pii=S1556086418332052&X-Amz-SignedHeaders=host&X-Amz-Security-Token=AgoJb3JpZ2luX2VjEDQaCXVzLWVhc3QtMSJHMEUCIQD8yynsTCFyNM13OG4a5yvDWZ%2BztTJ26heQnN9XHmVM2gIgcZAdkxja%2BJarFEaWPFaKCHDomt3j7ueaJW8lE6Fpmucq4wMIzP%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FARACGgwwNTkwMDM1NDY4NjUiDK9GlLRdF8%2BOBV%2F4LSq3A%2B8yIm6jTvhTCO%2BTN1UO2f2EesFL0izQHXQhu%2BFV5T37lQAaTDTqNNhPMdPvxYppQSrbUQ1bFKWQq6kgmIp%2Bvof2Wb5h3vZ2EQpg6IZ3QH4Sg8ntdnx0XK9xC5Zigyyn5oCc753Ap3GTwfBqb%2Fw%2B7lZ55hYUlKoPGxCPuHr9GfHH0DIN%2F9pdv%2BqU1KmiLWhWkBV1aYEbogvDV2CpO3%2FRT1SYQZzoeb8a9fBB5Pd6%2FqOYWs1vd7Mg8Dmp6oWRs6dkEFyPYBKMnWerFqNiidUv5NkPzgpNwV2rRzVU35Z0zxoGwecPAPbg42bTiZFzo9RYCbVHiKtSAK3enWVYcDYibzucmkqH2%2Be0sYiLPIch1WUOY6paTaTwomJdtemlmKmsJa9LTlTaQe4ak%2Bnunaw2T1mIOtbZjXatTZ2NvHMBW263r73aiZ8jgzOH4xPktYeHzAkwIs2oKUKMFH1CgHB9eiPq%2F63WlayX82tX2Xlw6xxZbiJfsj5fWR8ZMrc3ndBClSMyYXlH0ifa3%2BtvJkW8MANTbrFebrXGAWHRtpz3vnpgh2HhRR7dZ3h81%2Beki%2Frx2FJ2nCSRQdowlI746gU6tAF2WSVkNDlyo5SYJ4fXhwhdSE1Y1o67gTnbRQ9GHrFcd9Y7sXJwL5EUMvBoQLnr2mun7vvUqDrfjs5mxwpQ63fohvf9W%2Fj6OjdBHx9GEXiUgJ6OFUFBqfuqsgg31eCYQOnP3XLeKfBO%2FLncX0fwc9LVddU54Ting8434hFHS5E2PZQmDBp%2BWq8GX%2Bbvxlc2V88MccfV8EeUZvzoGqCXtHByR6L2Xif4BMwVm1Ia8pFdNOh9gBA%3D&host=68042c943591013ac2b2430a89b270f6af2c76d8dfd086a07176afe7c76c2c61&X-Amz-Expires=299&hash=223a7cf11d9e5b0764afae994d31cbb41fab36290ca7ce5e056218603c7e4c78
No data is associated with this publication.
Abstract

INTRODUCTION:Genomic profiling informs selection of matched targeted therapies as part of routine clinical care in NSCLC. Tissue biopsy is the criterion standard; however, genomic profiling of blood-derived circulating tumor DNA (ctDNA) has emerged as a minimally invasive alternative. METHODS:Hybrid capture-based genomic profiling of 62 genes was performed on blood-based ctDNA from 1552 patients with NSCLC. RESULTS:Evidence of ctDNA was detected in 80% of samples, and in 86% of these cases, at least one reportable genomic alteration (GA) was detected. Frequently altered genes were tumor protein p53 gene (TP53) (59%), EGFR (25%), and KRAS (17%). Comparative analysis with a tissue genomic database (N = 21,500) showed similar frequencies of GAs per gene, although KRAS mutation and EGFR T790M were more frequent in tissue and ctDNA, respectively (both p < 0.0001), likely reflecting the use of liquid versus tissue biopsy after relapse during targeted therapy. In temporally matched ctDNA and tissue samples from 33 patients with evidence of ctDNA in their blood, 64% of GAs detected in tissue were also detected in ctDNA, including 78% of short variants (58 of 74) and 100% of rearrangements (four of four), but only 16% of amplifications (four of 25). CONCLUSIONS:Genomic profiling of ctDNA detected clinically relevant GAs in a significant subset of NSCLC cases. Most alterations detected in matched tissue were also detected in ctDNA. These results suggest the utility of ctDNA testing in advanced NSCLC as a complementary approach to tissue testing. Blood-based ctDNA testing may be particularly useful at the time of progression during targeted therapy.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item