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Transl Cancer Res
2020 Jul 01;97:4341-4353. doi: 10.21037/tcr-19-1314.
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Screening of significant oncogenic changes in air pollution-related lung cancer in Chinese population.
Kanwal M
,
Ding X
,
Lin W
,
Cao Y
.
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BACKGROUND: Air pollution-related lung cancer has been considered as a deteriorating public health problem worldwide, particularly in developing countries. The highly air polluted regions in China particularly Xuanwei and Fuyuan counties have markedly high lung cancer rates and are considered as good models to study air pollution-related lung cancer. The present study investigated the clinically significant oncogenes in air pollution-related lung cancers.
METHODS: A combination of reverse transcriptase PCR (RT-PCR) and DNA sequencing was applied to examine the expression, mutations, or fusions of target genes, including human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), and cluster of differentiation 74-ROS proto-oncogene 1 (CD74-ROS1).
RESULTS: Of the 82 patients with lung cancer, 20.7% (17/82) exhibited HER2 up-regulation, and 1.2% (1/82) harbored HER2 insertion at exon 20. HER2 overexpression was not associated with air pollution levels and smoking status. A total of 6.1% (5/82) samples exhibited ALK gene rearrangements; two belonged to EML4-E2 + ALK-E20 and three were EML4-E13 + ALK-E20; all the five cases occurred either in smokers or in patients from the most air-polluted region. A total of 3.6% (3/82) carried the CD74-ROS1 fusion gene (CD74-E6 + ROS1-E34); the fusion event was not statistically associated with air pollution levels.
CONCLUSIONS: The high rates of prevalence indicated in the present study suggest that the screening of HER2 overexpression and EML4-ALK fusion events may assist in guiding treatment in air pollution-related lung cancer; the RT-PCR-based test proposed in this study may be a useful tool in clinical applications to screen these genetic changes.
Figure 1. RT-PCR and DNA sequencing analyses of HER2 expression and mutations. (A) Electrophoresis results of HER2 overexpression in tumor samples using RT-PCR; (B) sequencing result of the novel mutation detected in a female patient with lung adenocarcinoma. P14, P58, P71, P86, and P92 represent sample numbers. RT-PCR, reverse transcription polymerase chain reaction; HER2, human epidermal growth factor receptor.
Figure 2. Association of HER2 overexpression, and EML4-ALK and CD74-ROS1 fusion genes with air pollution (A), smoking (B), and total exposure (C). Low air pollution, living in relatively clean region C (Bap concentration, <60 ng/m3); High air pollution, living in heavily polluted regions A (Bap concentration, >170 ng/m3)/B (Bap concentration, 60–170 ng/m3). Low total exposure, living in relatively clean region C and also non-smoking; high total exposure, living in heavily polluted regions A/B or smoking. HER2, human epidermal growth factor receptor; EML4-ALK, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase; CD74-ROS1, cluster of differentiation 74-ROS proto-oncogene 1; Bap, benzo(a)pyrene.
Figure 3. RT-PCR analysis of EML4-ALK and CD74-ROS1 fusion genes. (A) Graphical representation of EML4-ALK fusion gene; (B) electrophoresis results of EML4-ALK fusion gene in tumor tissue samples and cell line. Fragment size of 550 bp represent variant 5b in EML4-E2+ALK-E20, whereas fragment size of 1,100 bp represent variant 2 in EML4-E13+ALK-E20; (C) graphical representation of CD74-ROS1 fusion gene; (D) electrophoresis results of CD74-ROS1 fusion gene in tumor samples. RT-PCR, reverse transcription polymerase chain reaction; EML4-ALK, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase; CD74-ROS1, cluster of differentiation 74-ROS proto-oncogene 1. E, exon. P45, P50, P11, P22, P37, P71, P41, and P66 represent sample numbers.
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