Fang Wang1, Shao-Yan Xi2, Wen-Wen Hao3, Xin-Hua Yang4, Ling Deng5, Yu-Xia Xu6, Xiao-Yan Wu7, Liang Zeng8, Kai-Hua Guo9, Hai-Yun Wang10. 1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: wangfang@sysucc.org.cn. 2. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: xshy@sysucc.org.cn. 3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangdong Key Laboratory Of Nasopharyngeal Carcinoma Diagnosis And Therapy, Guangzhou 510060, PR China. Electronic address: haoww@sysucc.org.cn. 4. Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: yangxh@sysucc.org.cn. 5. Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: dengling@sysucc.org.cn. 6. Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: xuyx@sysucc.org.cn. 7. Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China. Electronic address: wuxiaoy@sysucc.org.cn. 8. Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, PR China. Electronic address: zlxx03@126.com. 9. Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, PR China. Electronic address: guokh@mail.sysu.edu.cn. 10. Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, PR China; Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623 Guangdong, PR China. Electronic address: wanghy29@mail3.sysu.edu.cn.
Abstract
OBJECTIVES: Primary pulmonary salivary gland-type tumors (PSGTs) mainly comprise of mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), which are rare and molecularly poorly understood. This study aimed to profile the molecular alterations of PSGTs via targeted next-generation sequencing (NGS). MATERIAL AND METHODS: Immunohistochemistry was used to screen PSGTs in 32 patients and MAML2 and MYB rearrangements were detected using fluorescence in situ hybridization. 1021-Genepanel of targeted NGS was conducted to profile genomic mutations in all the PSGT patients. RESULTS: Among the 32 patients, 25 had MEC and 7 had ACC. MAML2 and MYB rearrangements were detected in 80.0% (20/25) of the MEC and 71.4% (5/7) of the ACC patients. Among the MEC patients, 10 (40.0%) had ≥1 mutation, and 6 of them had 11 isolated mutations with abundance >5%, namely NFE2L2, MYOD1, INPP4B, CCND2, SNTG1, HSPD1, TGFBR1, RBM10, NOTCH4, ASXL1, and PTPRD mutations. The remaining 4 patients had 9 mutations with abundance <5%, namely KMT2A, PDCD11, FLT1, BRCA2, APC, SLX4, FOXP1, FGFR1, and HRAS mutations. All the ACC patients had mutations, which were enriched in 5 pathways including the PI3K and NOTCH pathways, chromatin and cytoskeleton remodeling, and DNA damage. These results explain PSGTs harbor distinct driver features of MAML2 or MYB rearrangement, accompanied with wide mutational diversity with very low rate of somatic mutation. Several important pathways, including the NOTCH and PI3K pathways, and chromatin remodeling could be targeted to improve the survival in patients with ACC.
OBJECTIVES:Primary pulmonary salivary gland-type tumors (PSGTs) mainly comprise of mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), which are rare and molecularly poorly understood. This study aimed to profile the molecular alterations of PSGTs via targeted next-generation sequencing (NGS). MATERIAL AND METHODS: Immunohistochemistry was used to screen PSGTs in 32 patients and MAML2 and MYB rearrangements were detected using fluorescence in situ hybridization. 1021-Genepanel of targeted NGS was conducted to profile genomic mutations in all the PSGT patients. RESULTS: Among the 32 patients, 25 had MEC and 7 had ACC. MAML2 and MYB rearrangements were detected in 80.0% (20/25) of the MEC and 71.4% (5/7) of the ACC patients. Among the MEC patients, 10 (40.0%) had ≥1 mutation, and 6 of them had 11 isolated mutations with abundance >5%, namely NFE2L2, MYOD1, INPP4B, CCND2, SNTG1, HSPD1, TGFBR1, RBM10, NOTCH4, ASXL1, and PTPRD mutations. The remaining 4 patients had 9 mutations with abundance <5%, namely KMT2A, PDCD11, FLT1, BRCA2, APC, SLX4, FOXP1, FGFR1, and HRAS mutations. All the ACC patients had mutations, which were enriched in 5 pathways including the PI3K and NOTCH pathways, chromatin and cytoskeleton remodeling, and DNA damage. These results explain PSGTs harbor distinct driver features of MAML2 or MYB rearrangement, accompanied with wide mutational diversity with very low rate of somatic mutation. Several important pathways, including the NOTCH and PI3K pathways, and chromatin remodeling could be targeted to improve the survival in patients with ACC.
Authors: Xiaolin Sun; Weiqing Gu; Hui Yuan; Siyun Wang; Yang Yang; Laura Evangelista; Liyan Zhang; Lei Jiang Journal: Transl Lung Cancer Res Date: 2022-08