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Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients
Sequencing of the mutant allele fraction of circulating cell-free DNA (cfDNA) derived from tumors is increasingly utilized to detect actionable genomic alterations in cancer. We conducted a prospective blinded study of a comprehensive cfDNA sequencing panel with 54 cancer genes. To evaluate the conc...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741900/ https://www.ncbi.nlm.nih.gov/pubmed/26452027 |
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author | Kim, Seung Tae Lee, Won Suk Lanman, Richard B. Mortimer, Stefanie Zill, Oliver A. Kim, Kyoung-Mee Jang, Kee Taek Kim, Seok-Hyung Park, Se Hoon Park, Joon Oh Park, Young Suk Lim, Ho Yeong Eltoukhy, Helmy Kang, Won Ki Lee, Woo Yong Kim, Hee-Cheol Park, Keunchil Lee, Jeeyun Talasaz, AmirAli |
author_facet | Kim, Seung Tae Lee, Won Suk Lanman, Richard B. Mortimer, Stefanie Zill, Oliver A. Kim, Kyoung-Mee Jang, Kee Taek Kim, Seok-Hyung Park, Se Hoon Park, Joon Oh Park, Young Suk Lim, Ho Yeong Eltoukhy, Helmy Kang, Won Ki Lee, Woo Yong Kim, Hee-Cheol Park, Keunchil Lee, Jeeyun Talasaz, AmirAli |
author_sort | Kim, Seung Tae |
collection | PubMed |
description | Sequencing of the mutant allele fraction of circulating cell-free DNA (cfDNA) derived from tumors is increasingly utilized to detect actionable genomic alterations in cancer. We conducted a prospective blinded study of a comprehensive cfDNA sequencing panel with 54 cancer genes. To evaluate the concordance between cfDNA and tumor DNA (tDNA), sequencing results were compared between cfDNA from plasma and genomic tumor DNA (tDNA). Utilizing next generation digital sequencing technology (DST), we profiled approximately 78,000 bases encoding 512 complete exons in the targeted genes in cfDNA from plasma. Seventy-five patients were prospectively enrolled between February 2013 and March 2014, including 61 metastatic cancer patients and 14 clinical stage II CRC patients with matched plasma and tissue samples. Using the 54-gene panel, we detected at least one somatic mutation in 44 of 61 tDNA (72.1%) and 29 of 44 (65.9%) cfDNA. The overall concordance rate of cfDNA to tDNA was 85.9%, when all detected mutations were considered. We collected serial cfDNAs during cetuximab-based treatment in 2 metastatic KRAS wild-type CRC patients, one with acquired resistance and one with primary resistance. We demonstrate newly emerged KRAS mutation in cfDNA 1.5 months before radiologic progression. Another patient had a newly emerged PIK3CA H1047R mutation on cfDNA analysis at progression during cetuximab/irinotecan chemotherapy with gradual increase in allele frequency from 0.8 to 2.1%. This blinded, prospective study of a cfDNA sequencing showed high concordance to tDNA suggesting that the DST approach may be used as a non-invasive biopsy-free alternative to conventional sequencing using tumor biopsy. |
format | Online Article Text |
id | pubmed-4741900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47419002016-03-23 Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients Kim, Seung Tae Lee, Won Suk Lanman, Richard B. Mortimer, Stefanie Zill, Oliver A. Kim, Kyoung-Mee Jang, Kee Taek Kim, Seok-Hyung Park, Se Hoon Park, Joon Oh Park, Young Suk Lim, Ho Yeong Eltoukhy, Helmy Kang, Won Ki Lee, Woo Yong Kim, Hee-Cheol Park, Keunchil Lee, Jeeyun Talasaz, AmirAli Oncotarget Clinical Research Paper Sequencing of the mutant allele fraction of circulating cell-free DNA (cfDNA) derived from tumors is increasingly utilized to detect actionable genomic alterations in cancer. We conducted a prospective blinded study of a comprehensive cfDNA sequencing panel with 54 cancer genes. To evaluate the concordance between cfDNA and tumor DNA (tDNA), sequencing results were compared between cfDNA from plasma and genomic tumor DNA (tDNA). Utilizing next generation digital sequencing technology (DST), we profiled approximately 78,000 bases encoding 512 complete exons in the targeted genes in cfDNA from plasma. Seventy-five patients were prospectively enrolled between February 2013 and March 2014, including 61 metastatic cancer patients and 14 clinical stage II CRC patients with matched plasma and tissue samples. Using the 54-gene panel, we detected at least one somatic mutation in 44 of 61 tDNA (72.1%) and 29 of 44 (65.9%) cfDNA. The overall concordance rate of cfDNA to tDNA was 85.9%, when all detected mutations were considered. We collected serial cfDNAs during cetuximab-based treatment in 2 metastatic KRAS wild-type CRC patients, one with acquired resistance and one with primary resistance. We demonstrate newly emerged KRAS mutation in cfDNA 1.5 months before radiologic progression. Another patient had a newly emerged PIK3CA H1047R mutation on cfDNA analysis at progression during cetuximab/irinotecan chemotherapy with gradual increase in allele frequency from 0.8 to 2.1%. This blinded, prospective study of a cfDNA sequencing showed high concordance to tDNA suggesting that the DST approach may be used as a non-invasive biopsy-free alternative to conventional sequencing using tumor biopsy. Impact Journals LLC 2015-10-05 /pmc/articles/PMC4741900/ /pubmed/26452027 Text en Copyright: © 2015 Kim et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Clinical Research Paper Kim, Seung Tae Lee, Won Suk Lanman, Richard B. Mortimer, Stefanie Zill, Oliver A. Kim, Kyoung-Mee Jang, Kee Taek Kim, Seok-Hyung Park, Se Hoon Park, Joon Oh Park, Young Suk Lim, Ho Yeong Eltoukhy, Helmy Kang, Won Ki Lee, Woo Yong Kim, Hee-Cheol Park, Keunchil Lee, Jeeyun Talasaz, AmirAli Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients |
title | Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients |
title_full | Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients |
title_fullStr | Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients |
title_full_unstemmed | Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients |
title_short | Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients |
title_sort | prospective blinded study of somatic mutation detection in cell-free dna utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients |
topic | Clinical Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741900/ https://www.ncbi.nlm.nih.gov/pubmed/26452027 |
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