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Cancer Sci. 2017 Dec;108(12):2487-2494. doi: 10.1111/cas.13410. Epub 2017 Oct 20.

Comprehensive genomic profiling of lung cancer using a validated panel to explore therapeutic targets in East Asian patients.

Liu L1,2, Liu J3, Shao D3,4, Deng Q1,2, Tang H1,2, Liu Z3, Chen X1,5, Guo F3, Lin Y6, Mao M3, Kristiansen K3,4, Ye M3,4, He J1,5.

Author information

1
State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, Guangzhou, China.
2
The Translational Medicine Laboratory, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
3
BGI-Shenzhen, Shenzhen, China.
4
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
5
Department of Thoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
6
Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Abstract

People of East Asian ethnicity have a different prevalence of and show unique clinical characteristics and tumor histology of oncogenic mutations. However, only limited studies have explored the landscape of genomic alterations in lung adenocarcinoma derived from Asian patients thus far. In this single-center study, with an aim to elucidate the mutational profile of lung cancer in people of Chinese ethnicity and to use the obtained information to guide decision-making for treatment, we employed a well-validated assay to perform comprehensive genomic characterization of tumor specimens from 306 Chinese lung cancer patients. A total of 845 individual genomic alterations were found in 145 tumor-related genes with a median of 2.8 alterations (range: 1-18) per sample. The most frequently mutated genes were EGFR (46.7%), TP53 (21.2%), ALK (12.1%; 8.8% of mutation and 3.3% of rearrangement) and KRAS (10.1%). Upon comparison with the Cancer Genome Atlas dataset, we found that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS was only found in 10.1% of our Chinese patients. Clinically relevant genomic alterations were identified in 185 (60.5%) patients, including 50% in adenocarcinoma patients and 14% in squamous cell carcinoma patients. Our findings suggest that the Asian ethnicity is significantly different from the Caucasian ethnicity with regard to the presence of somatic driver mutations. Furthermore, we showed that the use of a comprehensive genotyping approach could help identify actionable genomic alterations that have potential impact on therapeutic decisions.

KEYWORDS:

Actionable genomic alteration; comprehensive genomic profiling; lung cancer; next generation sequencing; targeted therapy

PMID:
28949084
PMCID:
PMC5715245
DOI:
10.1111/cas.13410
[Indexed for MEDLINE]
Free PMC Article

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