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J Thorac Dis. 2018 Apr;10(Suppl 7):S820-S829. doi: 10.21037/jtd.2018.04.09.

Comprehensive targeted super-deep next generation sequencing enhances differential diagnosis of solitary pulmonary nodules.

Author information

1
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, Guangzhou 510006, China.
2
The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou 510120, China.
3
BGI-Guangzhou, Guangzhou Key Laboratory of Cancer Trans-Omics Research, Guangzhou 510006, China.
4
BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China.
5
Department of Biology, University of Copenhagen, Copenhagen, Denmark.
6
Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.
7
Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin 300308, China.

Abstract

Background:

A non-invasive method to predict the malignancy of surgery-candidate solitary pulmonary nodules (SPN) is urgently needed.

Methods:

Super-depth next generation sequencing (NGS) of 35 paired tissues and plasma DNA was performed as an attempt to develop an early diagnosis approach.

Results:

Only ~6% of malignant nodule patients had driver mutations in the circulating tumour DNA (ctDNA) with >10,000-fold sequencing depth, and the concordance of mutation between tDNA and ctDNA was 3.9%. The first innovative whole mutation scored model in this study predicted 33.3% of malignant SPN with 100% specificity.

Conclusions:

These results showed that lung cancer gene-targeted deep capture sequencing is not efficient enough to achieve ideal sensitivity by simply increasing the sequencing depth of ctDNA from early candidates. The sequencing could not be evaluated hotspot mutations in the early tumour stage. Nevertheless, a larger cohort is required to optimize this model, and more techniques may be incorporated to benefit the SPN high-risk population.

KEYWORDS:

Solid pulmonary nodule; circulating tumour DNA (ctDNA); early diagnosis; lung cancer; tumor mutational burden (TMB)

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

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