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Journal of Cancer Research and Clinical Oncology

Erschienen in:

06.11.2019 | Original Article – Clinical Oncology

Co-occurring genetic alterations and primary EGFR T790M mutations detected by NGS in pre-TKI-treated NSCLCs

verfasst von: Yuan Tang, Nanying Che, Yang Yu, Yun Gao, Huaiyin Shi, Qin Feng, Bing Wei, Liheng Ma, Min Gao, Jie Ma, Dongmei Lin

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2020

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Abstract

Introduction

Next-generation sequencing (NGS)-based assays to understand various mutations and co-occurrence of genomic alterations in non-small cell lung cancer (NSCLC) have enabled understanding of treatment impact on clinical outcomes.

Methods

This retrospective study was conducted in 1353 formalin-fixed paraffin-embedded (FFPE) tissues from surgically resected, pre-TKI-treated NSCLC patients with identified gene alterations. Genomic DNA and RNA extraction was followed by NGS library preparation and sequencing using the Ion Ampliseq Colon and Lung Cancer Gene Panel V2 and the AmpliSeq RNA Lung Cancer Research Fusion Panel.

Results

A total of 2328 alterations in 25 genes were detected from the 1293 patients. DNA mutations and RNA fusions co-occurred in 27 patients with TP53 being the most common co-occurring DNA mutation (43.8%) with concurrent ALK fusions. Analysis of the 975 patients with EGFR mutations revealed that the incidence of dual EGFR L858R/T790M mutations was higher compared to EGFR 19del/T790M, and the mean allele fraction (MAF) of T790M was lower compared to 19del in dual EGFR 19del/T790M patients.

Conclusion

NSCLC patients represented genetically heterogeneous subgroup with a high frequency of co-occurring mutations in cancer-associated pathways. This diverse mutational profile may have key clinical and research implications for understanding the variability of treatment outcome in pre-TKI-treated NSCLC population. The differences in the MAF of EGFR T790M may determine different responses to TKI therapy in patients harboring dual mutations.

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Titel: Co-occurring genetic alterations and primary EGFR T790M mutations detected by NGS in pre-TKI-treated NSCLCs
verfasst von: Yuan Tang
Nanying Che
Yang Yu
Yun Gao
Huaiyin Shi
Qin Feng
Bing Wei
Liheng Ma
Min Gao
Jie Ma
Dongmei Lin
Publikationsdatum: 06.11.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2020
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03065-0

Springer Medizin

Co-occurring genetic alterations and primary EGFR T790M mutations detected by NGS in pre-TKI-treated NSCLCs