Mutational landscape of primary pulmonary salivary gland-type tumors through targeted next-generation sequencing
| Autor: | Yuxia Xu, Xin-Hua Yang, Wen-Wen Hao, Xiao-yan Wu, Ling Deng, Shao-Yan Xi, Liang Zeng, Kai-Hua Guo, Fang Wang, Hai-Yun Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
Cancer Research Lung Neoplasms Adenoid cystic carcinoma medicine.disease_cause DNA sequencing Salivary Glands Minor Histocompatibility Antigens Phosphatidylinositol 3-Kinases Mucoepidermoid carcinoma medicine Biomarkers Tumor Humans MYB In Situ Hybridization Fluorescence Mutation Salivary gland medicine.diagnostic_test business.industry High-Throughput Nucleotide Sequencing Nuclear Proteins RNA-Binding Proteins Forkhead Transcription Factors medicine.disease Repressor Proteins medicine.anatomical_structure Oncology Cancer research Immunohistochemistry Carcinoma Mucoepidermoid business Fluorescence in situ hybridization |
| Zdroj: | Lung cancer (Amsterdam, Netherlands). 160 |
| ISSN: | 1872-8332 |
| Popis: | 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).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.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 abundance5%, namely NFE2L2, MYOD1, INPP4B, CCND2, SNTG1, HSPD1, TGFBR1, RBM10, NOTCH4, ASXL1, and PTPRD mutations. The remaining 4 patients had 9 mutations with abundance5%, 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. |
| Databáze: | OpenAIRE |
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