Deep sequencing of pericarcinomatous and tumor tissues is necessary to confirm whether pericarcinomatous tissue of non-small cell lung cancer (NSCLC) can serve as genetic background filter in next-generation sequencing (NGS) analysis.
181 multi-region tumor tissues from 32 operative NSCLC cases with matched pericarcinomatous tissues (at least 5cm from the tumor) were obtained for deep NSG (mean effective depth 810×) by a pan-cancer 1021-gene panel. Matched peripheral blood leucocytes were used as genetic filters. If the somatic genetic alteration was shared by all the tissue regions, it was defined as trunk mutation. Otherwise, it was called branch mutation. The genetic variation in pericarcinomatous tissues will be determined as tumor-derived mutation if it meet one of the following criteria: i) variant allele frequency ≥ 1%, ii) variant allele read number ≥ 5.
Of the 32 enrolled patients (EGFR+ adenocarcinoma, ADC, n = 9; KRAS+ ADC, n = 6; wild-type ADC, n = 11; squamous cell carcinoma and others, n = 6), tumor-derived mutations were detected from pericarcinomatous tissues in six patients (6/32, 19%). Furthermore, the detection of tumor-derived mutations in pericarcinomatous tissue was significantly associated with smoking and older-age but not with molecular NSCLC subtype. According to a total of 27 tumor-derived mutations detected in pericarcinomatous tissues, trunk mutations had a significantly higher proportion compared with branch mutations (74% vs. 26%, P = 0.0174). Most frequent mutated genes in pericarcinomatous tissues were tumor suppressor genes (TSGs), such as TP53. Mutations in either EGFR and KRAS were not detected in any pericarcinomatous samples.
Tumor-derived mutations exist in pericarcinomatous tissues, especically in the elderly and smoking population, mostly enriched in trunk mutations and TSGs, while neither EGFR nor KRAS mutations were detected. It suggests that pericarcinomatous tissue can serve as a normal control for detecting target oncogenes in general, but should not be recommended as genetic background filter for intratumor heterogeneity analysis in the elderly and smoking population.
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Legal entity responsible for the study
Sun Yat-sen University Cancer Center.
This work was supported by the National Key R&D Program of China (Grant No. 2016YFC0905500, 2016YFC0905503), Science and Technology Program of Guangdong (Grant No. 2017B020227001, 2016A020215084), Science and Technology Program of Guangzhou (Grant No. 201607020031, 201400000001-2), Chinese National Natural Science Foundation Project (Grant No. 81772476, 81572659,81602011), Pearl River Nova Program of Guangzhou (Grant No. 201610010048), and National Natural Science Funds for Young Scholars of China (Grant No. 81502355).
All authors have declared no conflicts of interest.
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