Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA

Young Kwang Chae, Andrew A. Davis, Benedito A. Carneiro, Sunandana Chandra, Nisha Anjali Mohindra, Aparna Kalyan, Jason Kaplan, Maria Matsangou, Sachin Pai, Ricardo Costa, Borko Jovanovic, Massimo Cristofanilli, Leonidas C Platanias, Francis J. Giles

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Genomic analysis of tumor tissue is the standard technique for identifying DNA alterations in malignancies. Genomic analysis of circulating tumor cell-free DNA (cfDNA) represents a relatively non-invasive method of assessing genomic alterations using peripheral blood. We compared the concordance of genomic alterations between cfDNA and tissue biopsies in this retrospective study. Twenty-eight patients with advanced solid tumors with paired next-generation sequencing tissue and cfDNA biopsies were identified. Sixty-five genes were common to both assays. Concordance was defined as the presence or absence of the identical genomic alteration(s) in a single gene on both molecular platforms. Including all aberrations, the average number of alterations per patient for tissue and cfDNA analysis was 4.82 and 2.96, respectively. When eliminating alterations not detectable in the cfDNA assay, mean number of alterations for tissue and cfDNA was 3.21 and 2.96, respectively. Overall, concordance was 91.9-93.9%. However, the concordance rate decreased to 11.8-17.1% when considering only genes with reported genomic alterations in either assay. Over 50% of mutations detected in either technique were not detected using the other biopsy technique, indicating a potential complementary role of each assay. Across 5 genes (TP53, EGFR, KRAS, APC, CDKN2A), sensitivity and specificity were 59.1% and 94.8%, respectively. Potential explanations for the lack of concordance include differences in assay platform, spatial and temporal factors, tumor heterogeneity, interval treatment, subclones, and potential germline DNA contamination. These results highlight the importance of prospective studies to evaluate concordance of genomic findings between distinct platforms that ultimately may inform treatment decisions.

Original languageEnglish (US)
Pages (from-to)65364-65373
Number of pages10
JournalOncotarget
Volume7
Issue number40
DOIs
StatePublished - Jan 1 2016

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DNA
Neoplasms
Biopsy
DNA Contamination
Genes
erbB-1 Genes
Circulating Neoplastic Cells
p53 Genes
Retrospective Studies
Prospective Studies
Sensitivity and Specificity
Mutation
Therapeutics

Keywords

  • Cell-free DNA
  • Genomic alterations
  • Lung cancer
  • Metastatic disease
  • Next-generation sequencing

ASJC Scopus subject areas

  • Oncology

Cite this

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title = "Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA",
abstract = "Genomic analysis of tumor tissue is the standard technique for identifying DNA alterations in malignancies. Genomic analysis of circulating tumor cell-free DNA (cfDNA) represents a relatively non-invasive method of assessing genomic alterations using peripheral blood. We compared the concordance of genomic alterations between cfDNA and tissue biopsies in this retrospective study. Twenty-eight patients with advanced solid tumors with paired next-generation sequencing tissue and cfDNA biopsies were identified. Sixty-five genes were common to both assays. Concordance was defined as the presence or absence of the identical genomic alteration(s) in a single gene on both molecular platforms. Including all aberrations, the average number of alterations per patient for tissue and cfDNA analysis was 4.82 and 2.96, respectively. When eliminating alterations not detectable in the cfDNA assay, mean number of alterations for tissue and cfDNA was 3.21 and 2.96, respectively. Overall, concordance was 91.9-93.9{\%}. However, the concordance rate decreased to 11.8-17.1{\%} when considering only genes with reported genomic alterations in either assay. Over 50{\%} of mutations detected in either technique were not detected using the other biopsy technique, indicating a potential complementary role of each assay. Across 5 genes (TP53, EGFR, KRAS, APC, CDKN2A), sensitivity and specificity were 59.1{\%} and 94.8{\%}, respectively. Potential explanations for the lack of concordance include differences in assay platform, spatial and temporal factors, tumor heterogeneity, interval treatment, subclones, and potential germline DNA contamination. These results highlight the importance of prospective studies to evaluate concordance of genomic findings between distinct platforms that ultimately may inform treatment decisions.",
keywords = "Cell-free DNA, Genomic alterations, Lung cancer, Metastatic disease, Next-generation sequencing",
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Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA. / Chae, Young Kwang; Davis, Andrew A.; Carneiro, Benedito A.; Chandra, Sunandana; Mohindra, Nisha Anjali; Kalyan, Aparna; Kaplan, Jason; Matsangou, Maria; Pai, Sachin; Costa, Ricardo; Jovanovic, Borko; Cristofanilli, Massimo; Platanias, Leonidas C; Giles, Francis J.

In: Oncotarget, Vol. 7, No. 40, 01.01.2016, p. 65364-65373.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Concordance between genomic alterations assessed by next-generation sequencing in tumor tissue or circulating cell-free DNA

AU - Chae, Young Kwang

AU - Davis, Andrew A.

AU - Carneiro, Benedito A.

AU - Chandra, Sunandana

AU - Mohindra, Nisha Anjali

AU - Kalyan, Aparna

AU - Kaplan, Jason

AU - Matsangou, Maria

AU - Pai, Sachin

AU - Costa, Ricardo

AU - Jovanovic, Borko

AU - Cristofanilli, Massimo

AU - Platanias, Leonidas C

AU - Giles, Francis J.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Genomic analysis of tumor tissue is the standard technique for identifying DNA alterations in malignancies. Genomic analysis of circulating tumor cell-free DNA (cfDNA) represents a relatively non-invasive method of assessing genomic alterations using peripheral blood. We compared the concordance of genomic alterations between cfDNA and tissue biopsies in this retrospective study. Twenty-eight patients with advanced solid tumors with paired next-generation sequencing tissue and cfDNA biopsies were identified. Sixty-five genes were common to both assays. Concordance was defined as the presence or absence of the identical genomic alteration(s) in a single gene on both molecular platforms. Including all aberrations, the average number of alterations per patient for tissue and cfDNA analysis was 4.82 and 2.96, respectively. When eliminating alterations not detectable in the cfDNA assay, mean number of alterations for tissue and cfDNA was 3.21 and 2.96, respectively. Overall, concordance was 91.9-93.9%. However, the concordance rate decreased to 11.8-17.1% when considering only genes with reported genomic alterations in either assay. Over 50% of mutations detected in either technique were not detected using the other biopsy technique, indicating a potential complementary role of each assay. Across 5 genes (TP53, EGFR, KRAS, APC, CDKN2A), sensitivity and specificity were 59.1% and 94.8%, respectively. Potential explanations for the lack of concordance include differences in assay platform, spatial and temporal factors, tumor heterogeneity, interval treatment, subclones, and potential germline DNA contamination. These results highlight the importance of prospective studies to evaluate concordance of genomic findings between distinct platforms that ultimately may inform treatment decisions.

AB - Genomic analysis of tumor tissue is the standard technique for identifying DNA alterations in malignancies. Genomic analysis of circulating tumor cell-free DNA (cfDNA) represents a relatively non-invasive method of assessing genomic alterations using peripheral blood. We compared the concordance of genomic alterations between cfDNA and tissue biopsies in this retrospective study. Twenty-eight patients with advanced solid tumors with paired next-generation sequencing tissue and cfDNA biopsies were identified. Sixty-five genes were common to both assays. Concordance was defined as the presence or absence of the identical genomic alteration(s) in a single gene on both molecular platforms. Including all aberrations, the average number of alterations per patient for tissue and cfDNA analysis was 4.82 and 2.96, respectively. When eliminating alterations not detectable in the cfDNA assay, mean number of alterations for tissue and cfDNA was 3.21 and 2.96, respectively. Overall, concordance was 91.9-93.9%. However, the concordance rate decreased to 11.8-17.1% when considering only genes with reported genomic alterations in either assay. Over 50% of mutations detected in either technique were not detected using the other biopsy technique, indicating a potential complementary role of each assay. Across 5 genes (TP53, EGFR, KRAS, APC, CDKN2A), sensitivity and specificity were 59.1% and 94.8%, respectively. Potential explanations for the lack of concordance include differences in assay platform, spatial and temporal factors, tumor heterogeneity, interval treatment, subclones, and potential germline DNA contamination. These results highlight the importance of prospective studies to evaluate concordance of genomic findings between distinct platforms that ultimately may inform treatment decisions.

KW - Cell-free DNA

KW - Genomic alterations

KW - Lung cancer

KW - Metastatic disease

KW - Next-generation sequencing

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