eISSN: 2084-9869
ISSN: 1233-9687
Polish Journal of Pathology
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SCImago Journal & Country Rank
2/2021
vol. 72
 
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abstract:
Original paper

Plasma biopsy by Tag-sequencing: an acceptable alternative to tumor tissue profiling in non-small-cell lung cancer

Anurag Mehta
1
,
Sanjeev Kumar Sharma
2
,
Dushyant Kumar
2
,
Smreti Vasudevan
3

1.
Department of Laboratory and Transfusion Services and Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, India
2.
Molecular Laboratory, Department of Laboratory and Transfusion Services, Rajiv Gandhi Cancer Institute and Research Centre, India
3.
Department of Research, Rajiv Gandhi Cancer Institute and Research Centre, India
Pol J Pathol 2021; 72 (2): 117-123
Online publish date: 2021/09/30
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Tag-sequencing is a modified next-generation sequencing (NGS) approach wherein targeted regions are tagged with unique molecular identifiers enabling error-free detection of rare genomic alterations. We aimed to perform this high-

fidelity sequencing to identify actionable variants from the plasma of lung cancer patients.

Targeted sequencing was performed from plasma-derived cell-free nucleic acid in twenty-one advanced, treatment naïve, non-small-cell lung cancer (NSCLC) patients. Clinically significant genetic alterations were compared with matched tumor NGS profile for each patient (patient-level), and separately for each alteration (variant-level). Cross-platform validation was done for EGFR and KRAS mutations (real-time PCR) and ALK1 rearrangement (immunohistochemistry).

Forty-seven alterations (26 in plasma and 21 in tumor tissue) were detected in 19/21 tested cases. Overall-concordance between the two assays was 94.87%

(κ of 0.71, 95% CI: 0.54-0.89). Patient-level and genic-concordance was 57.1% (12/21 cases) and 67.86%, respectively. Almost perfect agreement was reached for detecting actionable EGFR mutations and ALK1 rearrangement (κ of 0.89 and

κ of 1, respectively), which was confirmed by single-gene testing.

Substantial agreement between the assays makes Tag-sequencing a viable option for identifying multibiomarkers from the plasma of advanced NSCLC patients in special circumstances where tissue has depleted/tumor is inaccessible/high risk of biopsy due to existing comorbidities.
keywords:

driver mutations in lung cancer, free-circulating nucleic acids, Tag-sequencing, liquid biopsy

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