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Whole Exome Sequencing of Cell-Free DNA for Early Lung Cancer: A Pilot Study to Differentiate Benign From Malignant CT-Detected Pulmonary Lesions.

Publication ,  Journal Article
Tailor, TD; Rao, X; Campa, MJ; Wang, J; Gregory, SG; Patz, EF
Published in: Front Oncol
2019

Introduction: Indeterminate pulmonary lesions (IPL) detected by CT pose a significant clinical challenge, frequently necessitating long-term surveillance or biopsy for diagnosis. In this pilot investigation, we performed whole exome sequencing (WES) of plasma cell free (cfDNA) and matched germline DNA in patients with CT-detected pulmonary lesions to determine the feasibility of somatic cfDNA mutations to differentiate benign from malignant pulmonary nodules. Methods: 33 patients with a CT-detected pulmonary lesions were retrospectively enrolled (n = 16 with a benign nodule, n = 17 with a malignant nodule). Following isolation and amplification of plasma cfDNA and matched peripheral blood mononuclear cells (PBMC) from patient blood samples, WES of cfDNA and PBMC DNA was performed. After genomic alignment and filtering, we looked for lung-cancer associated driver mutations and next identified high-confidence somatic variants in both groups. Results: Somatic cfDNA mutations were observed in both groups, with the cancer group demonstrating more variants than the benign group (1083 ± 476 versus 553 ± 519, p < 0.0046). By selecting variants present in >2 cancer patients and not the benign group, we accurately identified 82% (14/17) of cancer patients. Conclusions: This study suggests a potential role for cfDNA for the early identification of lung cancer in patients with CT-detected pulmonary lesions. Importantly, a substantial number of somatic variants in healthy patients with benign pulmonary nodules were also found. Such "benign" variants, while largely unexplored to date, have widespread relevance to all liquid biopsies if cfDNA is to be used accurately for cancer detection.

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Published In

Front Oncol

DOI

ISSN

2234-943X

Publication Date

2019

Volume

9

Start / End Page

317

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
  • 1112 Oncology and Carcinogenesis
 

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Tailor, T. D., Rao, X., Campa, M. J., Wang, J., Gregory, S. G., & Patz, E. F. (2019). Whole Exome Sequencing of Cell-Free DNA for Early Lung Cancer: A Pilot Study to Differentiate Benign From Malignant CT-Detected Pulmonary Lesions. Front Oncol, 9, 317. https://doi.org/10.3389/fonc.2019.00317
Tailor, Tina D., Xiayu Rao, Michael J. Campa, Jing Wang, Simon G. Gregory, and Edward F. Patz. “Whole Exome Sequencing of Cell-Free DNA for Early Lung Cancer: A Pilot Study to Differentiate Benign From Malignant CT-Detected Pulmonary Lesions.Front Oncol 9 (2019): 317. https://doi.org/10.3389/fonc.2019.00317.
Tailor, Tina D., et al. “Whole Exome Sequencing of Cell-Free DNA for Early Lung Cancer: A Pilot Study to Differentiate Benign From Malignant CT-Detected Pulmonary Lesions.Front Oncol, vol. 9, 2019, p. 317. Pubmed, doi:10.3389/fonc.2019.00317.

Published In

Front Oncol

DOI

ISSN

2234-943X

Publication Date

2019

Volume

9

Start / End Page

317

Location

Switzerland

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
  • 1112 Oncology and Carcinogenesis