Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens

B. Hannigan, W. Ye, M. Mehrotra, Vincent Lam, A. Bolivar, S. Zalles, B. A. Barkoh, D. Duose, P. C. Hu, R. Broaddus, J. Stewart, J. Heymach, L. J. Medeiros, I. Wistuba, R. Luthra, S. Roy-Chowdhuri

Research output: Contribution to journalArticle

Abstract

Introduction: Tumor mutation profiling is standard-of-care in lung carcinoma patients. However, comprehensive molecular profiling of small specimens, including core needle biopsy (CNB) and fine-needle aspiration (FNA) specimens, may often be inadequate due to limited tissue. Centrifuged FNA supernatants, which are typically discarded, have emerged recently as a novel liquid-based biopsy for molecular testing. In this study, we evaluate the use of lung carcinoma FNA supernatants for detecting clinically relevant mutations. Methods: Supernatants from lung carcinoma FNA samples (n = 150) were evaluated. Samples were further analyzed using next-generation sequencing (NGS) and ultrasensitive droplet digital PCR (ddPCR). Mutation profiles in a subset of samples were compared with results derived from paired tissue samples from the same patient (n = 67) and available plasma liquid biopsy assay (n = 45). Results: All 150 samples yielded adequate DNA and NGS were carried out successfully on 104 (90%) of 116 selected samples. Somatic mutations were detected in 82% of the samples and in 50% of these patients a clinically relevant mutation was identified that would qualify them for targeted therapy or a clinical trial. There was high overall concordance between the mutation profiles of supernatants and the corresponding tissue samples, with 100% concordance with concurrent FNA and 96% with concurrent CNB samples. Comparison of actionable driver mutations detected in supernatant versus plasma samples showed 84% concordance. Conclusions: FNA supernatants can provide a valuable specimen source for genotyping lung carcinoma especially in patients with insufficient tumor tissue, thereby reducing multigene mutation profiling failure rates, improving turnaround times, and avoiding repeat biopsies.

Original languageEnglish (US)
Article numbermdz102
Pages (from-to)963-969
Number of pages7
JournalAnnals of Oncology
Volume30
Issue number6
DOIs
StatePublished - Jun 1 2019

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Fine Needle Biopsy
Carcinoma
Biopsy
Lung
Mutation
Large-Core Needle Biopsy
Standard of Care
Neoplasms
Clinical Trials
Polymerase Chain Reaction
DNA

Keywords

  • fine-needle aspiration
  • liquid biopsy
  • lung cancer
  • mutation profiling
  • next-generation sequencing
  • supernatant

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Hannigan, B., Ye, W., Mehrotra, M., Lam, V., Bolivar, A., Zalles, S., ... Roy-Chowdhuri, S. (2019). Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens. Annals of Oncology, 30(6), 963-969. [mdz102]. https://doi.org/10.1093/annonc/mdz102

Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens. / Hannigan, B.; Ye, W.; Mehrotra, M.; Lam, Vincent; Bolivar, A.; Zalles, S.; Barkoh, B. A.; Duose, D.; Hu, P. C.; Broaddus, R.; Stewart, J.; Heymach, J.; Medeiros, L. J.; Wistuba, I.; Luthra, R.; Roy-Chowdhuri, S.

In: Annals of Oncology, Vol. 30, No. 6, mdz102, 01.06.2019, p. 963-969.

Research output: Contribution to journalArticle

Hannigan, B, Ye, W, Mehrotra, M, Lam, V, Bolivar, A, Zalles, S, Barkoh, BA, Duose, D, Hu, PC, Broaddus, R, Stewart, J, Heymach, J, Medeiros, LJ, Wistuba, I, Luthra, R & Roy-Chowdhuri, S 2019, 'Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens', Annals of Oncology, vol. 30, no. 6, mdz102, pp. 963-969. https://doi.org/10.1093/annonc/mdz102
Hannigan, B. ; Ye, W. ; Mehrotra, M. ; Lam, Vincent ; Bolivar, A. ; Zalles, S. ; Barkoh, B. A. ; Duose, D. ; Hu, P. C. ; Broaddus, R. ; Stewart, J. ; Heymach, J. ; Medeiros, L. J. ; Wistuba, I. ; Luthra, R. ; Roy-Chowdhuri, S. / Liquid biopsy assay for lung carcinoma using centrifuged supernatants from fine-needle aspiration specimens. In: Annals of Oncology. 2019 ; Vol. 30, No. 6. pp. 963-969.
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abstract = "Introduction: Tumor mutation profiling is standard-of-care in lung carcinoma patients. However, comprehensive molecular profiling of small specimens, including core needle biopsy (CNB) and fine-needle aspiration (FNA) specimens, may often be inadequate due to limited tissue. Centrifuged FNA supernatants, which are typically discarded, have emerged recently as a novel liquid-based biopsy for molecular testing. In this study, we evaluate the use of lung carcinoma FNA supernatants for detecting clinically relevant mutations. Methods: Supernatants from lung carcinoma FNA samples (n = 150) were evaluated. Samples were further analyzed using next-generation sequencing (NGS) and ultrasensitive droplet digital PCR (ddPCR). Mutation profiles in a subset of samples were compared with results derived from paired tissue samples from the same patient (n = 67) and available plasma liquid biopsy assay (n = 45). Results: All 150 samples yielded adequate DNA and NGS were carried out successfully on 104 (90{\%}) of 116 selected samples. Somatic mutations were detected in 82{\%} of the samples and in 50{\%} of these patients a clinically relevant mutation was identified that would qualify them for targeted therapy or a clinical trial. There was high overall concordance between the mutation profiles of supernatants and the corresponding tissue samples, with 100{\%} concordance with concurrent FNA and 96{\%} with concurrent CNB samples. Comparison of actionable driver mutations detected in supernatant versus plasma samples showed 84{\%} concordance. Conclusions: FNA supernatants can provide a valuable specimen source for genotyping lung carcinoma especially in patients with insufficient tumor tissue, thereby reducing multigene mutation profiling failure rates, improving turnaround times, and avoiding repeat biopsies.",
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AU - Hannigan, B.

AU - Ye, W.

AU - Mehrotra, M.

AU - Lam, Vincent

AU - Bolivar, A.

AU - Zalles, S.

AU - Barkoh, B. A.

AU - Duose, D.

AU - Hu, P. C.

AU - Broaddus, R.

AU - Stewart, J.

AU - Heymach, J.

AU - Medeiros, L. J.

AU - Wistuba, I.

AU - Luthra, R.

AU - Roy-Chowdhuri, S.

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Introduction: Tumor mutation profiling is standard-of-care in lung carcinoma patients. However, comprehensive molecular profiling of small specimens, including core needle biopsy (CNB) and fine-needle aspiration (FNA) specimens, may often be inadequate due to limited tissue. Centrifuged FNA supernatants, which are typically discarded, have emerged recently as a novel liquid-based biopsy for molecular testing. In this study, we evaluate the use of lung carcinoma FNA supernatants for detecting clinically relevant mutations. Methods: Supernatants from lung carcinoma FNA samples (n = 150) were evaluated. Samples were further analyzed using next-generation sequencing (NGS) and ultrasensitive droplet digital PCR (ddPCR). Mutation profiles in a subset of samples were compared with results derived from paired tissue samples from the same patient (n = 67) and available plasma liquid biopsy assay (n = 45). Results: All 150 samples yielded adequate DNA and NGS were carried out successfully on 104 (90%) of 116 selected samples. Somatic mutations were detected in 82% of the samples and in 50% of these patients a clinically relevant mutation was identified that would qualify them for targeted therapy or a clinical trial. There was high overall concordance between the mutation profiles of supernatants and the corresponding tissue samples, with 100% concordance with concurrent FNA and 96% with concurrent CNB samples. Comparison of actionable driver mutations detected in supernatant versus plasma samples showed 84% concordance. Conclusions: FNA supernatants can provide a valuable specimen source for genotyping lung carcinoma especially in patients with insufficient tumor tissue, thereby reducing multigene mutation profiling failure rates, improving turnaround times, and avoiding repeat biopsies.

AB - Introduction: Tumor mutation profiling is standard-of-care in lung carcinoma patients. However, comprehensive molecular profiling of small specimens, including core needle biopsy (CNB) and fine-needle aspiration (FNA) specimens, may often be inadequate due to limited tissue. Centrifuged FNA supernatants, which are typically discarded, have emerged recently as a novel liquid-based biopsy for molecular testing. In this study, we evaluate the use of lung carcinoma FNA supernatants for detecting clinically relevant mutations. Methods: Supernatants from lung carcinoma FNA samples (n = 150) were evaluated. Samples were further analyzed using next-generation sequencing (NGS) and ultrasensitive droplet digital PCR (ddPCR). Mutation profiles in a subset of samples were compared with results derived from paired tissue samples from the same patient (n = 67) and available plasma liquid biopsy assay (n = 45). Results: All 150 samples yielded adequate DNA and NGS were carried out successfully on 104 (90%) of 116 selected samples. Somatic mutations were detected in 82% of the samples and in 50% of these patients a clinically relevant mutation was identified that would qualify them for targeted therapy or a clinical trial. There was high overall concordance between the mutation profiles of supernatants and the corresponding tissue samples, with 100% concordance with concurrent FNA and 96% with concurrent CNB samples. Comparison of actionable driver mutations detected in supernatant versus plasma samples showed 84% concordance. Conclusions: FNA supernatants can provide a valuable specimen source for genotyping lung carcinoma especially in patients with insufficient tumor tissue, thereby reducing multigene mutation profiling failure rates, improving turnaround times, and avoiding repeat biopsies.

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