Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors
Introduction: Salivary gland carcinomas (SGC) are histologically diverse cancers and next-generation sequencing (NGS) to identify key molecular targets is an important aspect in the management of advanced cases. Methods: DNA was extracted from paraffin embedded tissues of advanced SGC and comprehens...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/2/519 |
| _version_ | 1797622141634478080 |
|---|---|
| author | Maroun Bou Zerdan Prashanth Ashok Kumar Daniel Zaccarini Jeffrey Ross Richard Huang Abirami Sivapiragasam |
| author_facet | Maroun Bou Zerdan Prashanth Ashok Kumar Daniel Zaccarini Jeffrey Ross Richard Huang Abirami Sivapiragasam |
| author_sort | Maroun Bou Zerdan |
| collection | DOAJ |
| description | Introduction: Salivary gland carcinomas (SGC) are histologically diverse cancers and next-generation sequencing (NGS) to identify key molecular targets is an important aspect in the management of advanced cases. Methods: DNA was extracted from paraffin embedded tissues of advanced SGC and comprehensive genomic profiling (CGP) was carried out to evaluate for base substitutions, short insertions, deletions, copy number changes, gene fusions and rearrangements. Tumor mutation burden (TMB) was calculated on approximately 1.25 Mb. Some 324 genes in the FoundationOne CDX panel were analyzed. Results: Mucoepidermoid carcinoma (MECa) mutations were assessed. CDKN2A and CDKN2B GA were common in mucoepidermoid carcinoma (MECa) (52.5 and 30.5%). PIK3CA was also common in MECa (16.9%). ERBB2 amplification/short variants (amp/SV) were found in MECa (5.9/0%). HRAS GA was common in MECa (14.4%) as well. Other targets, including BAP1, PTEN, and KRAS, were noted but had a low incidence. In terms of immunotherapy (IO)-predictive markers, TMB > 10 was more common in MECa (16.9%). PDL1 high was also seen in MECa (4.20%). Conclusion: SGC are rare tumors with no FDA-approved treatment options. This large dataset reveals many opportunities for IO and targeted therapy contributing to the continuously increased precision in the selection of treatment for these patients. |
| first_indexed | 2024-03-11T09:07:07Z |
| format | Article |
| id | doaj.art-932efb5fb3184e08a61d120d47d24558 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T09:07:07Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-932efb5fb3184e08a61d120d47d245582023-11-16T19:19:25ZengMDPI AGBiomedicines2227-90592023-02-0111251910.3390/biomedicines11020519Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma TumorsMaroun Bou Zerdan0Prashanth Ashok Kumar1Daniel Zaccarini2Jeffrey Ross3Richard Huang4Abirami Sivapiragasam5Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USADivision of Hematology/Oncology, Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USADepartment of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USAFoundation Medicine, Inc., Morrisville, NC 27560, USADepartment of Pathology, SUNY Upstate Medical University, Syracuse, NY 13210, USADivision of Hematology/Oncology, Department of Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USAIntroduction: Salivary gland carcinomas (SGC) are histologically diverse cancers and next-generation sequencing (NGS) to identify key molecular targets is an important aspect in the management of advanced cases. Methods: DNA was extracted from paraffin embedded tissues of advanced SGC and comprehensive genomic profiling (CGP) was carried out to evaluate for base substitutions, short insertions, deletions, copy number changes, gene fusions and rearrangements. Tumor mutation burden (TMB) was calculated on approximately 1.25 Mb. Some 324 genes in the FoundationOne CDX panel were analyzed. Results: Mucoepidermoid carcinoma (MECa) mutations were assessed. CDKN2A and CDKN2B GA were common in mucoepidermoid carcinoma (MECa) (52.5 and 30.5%). PIK3CA was also common in MECa (16.9%). ERBB2 amplification/short variants (amp/SV) were found in MECa (5.9/0%). HRAS GA was common in MECa (14.4%) as well. Other targets, including BAP1, PTEN, and KRAS, were noted but had a low incidence. In terms of immunotherapy (IO)-predictive markers, TMB > 10 was more common in MECa (16.9%). PDL1 high was also seen in MECa (4.20%). Conclusion: SGC are rare tumors with no FDA-approved treatment options. This large dataset reveals many opportunities for IO and targeted therapy contributing to the continuously increased precision in the selection of treatment for these patients.https://www.mdpi.com/2227-9059/11/2/519salivary gland tumorscomprehensive genomic profilingmucoepidermoid carcinomaimmunotherapynext-generation sequencing |
| spellingShingle | Maroun Bou Zerdan Prashanth Ashok Kumar Daniel Zaccarini Jeffrey Ross Richard Huang Abirami Sivapiragasam Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors Biomedicines salivary gland tumors comprehensive genomic profiling mucoepidermoid carcinoma immunotherapy next-generation sequencing |
| title | Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors |
| title_full | Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors |
| title_fullStr | Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors |
| title_full_unstemmed | Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors |
| title_short | Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors |
| title_sort | molecular targets in salivary gland cancers a comprehensive genomic analysis of 118 mucoepidermoid carcinoma tumors |
| topic | salivary gland tumors comprehensive genomic profiling mucoepidermoid carcinoma immunotherapy next-generation sequencing |
| url | https://www.mdpi.com/2227-9059/11/2/519 |
| work_keys_str_mv | AT marounbouzerdan moleculartargetsinsalivaryglandcancersacomprehensivegenomicanalysisof118mucoepidermoidcarcinomatumors AT prashanthashokkumar moleculartargetsinsalivaryglandcancersacomprehensivegenomicanalysisof118mucoepidermoidcarcinomatumors AT danielzaccarini moleculartargetsinsalivaryglandcancersacomprehensivegenomicanalysisof118mucoepidermoidcarcinomatumors AT jeffreyross moleculartargetsinsalivaryglandcancersacomprehensivegenomicanalysisof118mucoepidermoidcarcinomatumors AT richardhuang moleculartargetsinsalivaryglandcancersacomprehensivegenomicanalysisof118mucoepidermoidcarcinomatumors AT abiramisivapiragasam moleculartargetsinsalivaryglandcancersacomprehensivegenomicanalysisof118mucoepidermoidcarcinomatumors |