Status of 10 targeted genes of non-small cell lung cancer in eastern China: A study of 884 patients based on NGS in a single institution

Lung Cancer

Thorac Cancer. 2020 Jul 30. doi: 10.1111/1759-7714.13577. Online ahead of print.


BACKGROUND: The status of targeted genes and the association between targeted genes and clinicopathological features in Chinese lung cancer patients remains to be elucidated.

METHODS: The status of 10 targeted genes was evaluated by next-generation sequencing (NGS) in 884 non-small cell lung cancer (NSCLC) patients. The relationship between gene alterations and clinicopathological characters was analyzed.

RESULTS: Overall, 684 (77.4%) patients harbored gene alterations, and EGFR (510, 57.7%) was found to be the most common type of mutation followed by KRAS (91, 10.3%), HER2 (38, 4.3%), PIK3CA (32, 3.6%), ALK (21, 2.4%), BRAF (10, 1.1%), ROS1 (5, 0.6%), RET (5, 0.6%), MET (4, 0.5%) and NRAS (1, 0.1%). Gene alterations were more frequent in females, non-smokers and adenocarcinoma (P < 0.001). EGFR mutations were associated with women, non-smokers, normal level of serum tumor markers, and adenocarcinoma (P < 0.001). Patients without lymph node metastasis (P = 0.012), or early stage disease (P < 0.001) exhibited a higher EGFR mutation rate. KRAS mutations tended to arise in men (P < 0.001), smokers (P < 0.001) and patients with higher levels of serum tumor markers (P = 0.048). A mucus-producing component was associated with KRAS (P < 0.001), ROS1 (P = 0.033) and ALK (P < 0.001) alterations. ALK and ROS1 rearrangements were more frequent in micropapillary structures (P = 0.004, P = 0.012). BRAF mutation was associated with advanced disease patients and micropapillary structure (P < 0.001). PIK3CA mutation was more likely to be found in elderly patients (P = 0.014). Some patients had synchronous gene alterations, including EGFR/PIK3CA, EGFR/HER2, HER2/KRAS, EGFR/KRAS, EGFR/ROS1, EGFR/NRAS, KRAS/PIK3CA, KRAS/PIK3CA/HER2.

CONCLUSIONS: Most patients had at least one genetic alteration, and individual patients harbored synchronous mutation. Each gene alteration had unique clinicopathological characteristics.

KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: This study revealed the frequency and distribution of 10 targeted gene abnormalities and their association with clinicopathological parameters of Chinese non-small cell lung cancer (NSCLC) patients in eastern China.

WHAT THIS STUDY ADDS: Some rare synchronous mutations were detected in our study by next-generation sequencing (NGS).