The landscape of STK11 mutations and hotspots in Chinese patients with solid tumors.

Abstract

e15112 Background: STK11 is a tumor suppressor gene, and loss-of-function mutations are oncogenic, due to loss of AMPK regulation of mTOR and HIF-1-α. STK11 has been identified as a tumor suppressor in several types of cancers. Emerging evidence suggests that STK11 mutations may influence clinical outcome and response to immunotherapy in cancer. However, the genomic features of STK11 are obscured in Chinese solid tumors. In this study, we investigated the landscape of STK11 in Chinese patients with solid tumors. Methods: Next-generation targeted sequencing of major cancer-related 599 genes in a large cohort of 5420 Chinese solid tumors. Results: STK11 mutations were identified in 184 (3.39%, 184/5420) Chinese solid tumors patients. Although STK11 mutations are negligible in solid tumors, endometrial cancer patients (15.79%), esophagus and esophagogastric junction cancer (9.09%), ovarian cancer (4.92%), and lung cancer (4.92%) possess relatively high rates of STK11 mutation. However, STK11 alterations were not found in head and neck cancer, kidney cancer, and CNS tumor cases. A total of 194 mutation sites have been identified in STK11, including 43 pathogenic/ likely pathogenic mutations, the most prominent mutational hotspots are P281fs, D194Y, W308C, S216F, D53fs, and Y60, occupying almost 48.84% of all mutations in STK11. A total of 17 patients harbored copy number variations (CNV) of STK11 in Chinese solid tumors, mainly occurring in the neuroendocrine tumor, breast cancer, and gastric cancer. Conclusions: We found a unique genomic feature of STK11 in Chinese solid tumor patients. Our results show that STK11 may be a potential therapeutic target.