4.4 Article

Mutation Profile of Thymic Carcinoma and Thymic Neuroendocrine Tumor by Targeted Next-generation Sequencing

Journal

CLINICAL LUNG CANCER
Volume 22, Issue 2, Pages 92-+

Publisher

CIG MEDIA GROUP, LP
DOI: 10.1016/j.cllc.2020.11.010

Keywords

Next-generation sequence; Receptor tyrosine kinase; Targeted therapy; Thymic carcinoma; Thymic neuroendocrine tumor

Categories

Funding

  1. MEXT, Japan [20K17755]
  2. Grants-in-Aid for Scientific Research [20K17755] Funding Source: KAKEN

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The mutational profile of thymic carcinoma, including squamous cell carcinomas, was analyzed using next-generation sequencing. TP53, KIT, and PDGFRA were the most frequently mutated genes. Squamous cell carcinomas with mutations in receptor tyrosine kinases had significantly shorter survival time.
The mutational profile of thymic carcinoma still remains unclear. We analyzed 54 thymic carcinomas, including 44 squamous cell carcinomas, using a next-generation sequencing panel. The 3 most frequently mutated genes were TP53 (18.5%), KIT (7.4%), and PDGFRA (5.6%). The thymic squamous cell carcinomas with gene mutations in receptor tyrosine kinases exhibited significantly shorter overall survival time than those without (P [ .0481). Background: Thymic carcinoma is a rare mediastinal neoplasm, and little is known about its genetic variability, which has hampered the development of targeted therapies. Patients and Methods: We tested a next-generation sequencing panel containing 50 common cancer-related genes in 48 cases of thymic carcinoma and 6 cases of thymic neuroendocrine tumor. Results: We detected 42 variant calls in 21 of 54 cases. There was no significant difference in mutation frequency between thymic carcinoma and thymic neuroendocrine tumors. Among these, TP53 was the most frequently mutated gene (18.5%), followed by KIT (7.4%) and PDGFRA (5.6%). According to the gene pathways and groups, the p53 pathway, including TP53 and ATM, was most frequently affected (20.4%), followed by the receptor tyrosine kinase (RTK)/RAS pathway (18.5%) and PI3K pathway (5.6%). According to the OncoKB, an expert-guided precision oncology knowledge base, 7 genes among 10 cases (18.5%) were annotated with level 1 evidence, suggesting potentially therapeutic targets. Prognostic analyses, conducted in thymic squamous cell carcinomas, revealed that tumor cases harboring gene mutations in RTKs, including KIT (7.4%), PDGFRA (5.6%) and EGFR (3.7%), were significantly associated with a worse overall survival time (P = .0481). Among clinicopathologic factors, the advanced Masaoka stage was marginally associated with a worse overall survival (P = .0757). In the subsequent multivariate analysis, neither of the factors achieved statistical significance. Conclusions: In this preliminary next-generation sequencing study, we unexpectedly found evidence suggesting that several gene mutations might be therapeutic targets. The gene mutations in RTKs may be a valuable prognostic factor in thymic squamous cell carcinoma. The mutational profile of thymic carcinoma still remains unclear. We analyzed 54 thymic carcinomas, including 44 squamous cell carcinomas, using a next-generation sequencing panel. The 3 most frequently mutated genes were TP53 (18.5%), KIT (7.4%), and PDGFRA (5.6%). The thymic squamous cell carcinomas with gene mutations in receptor tyrosine kinases exhibited significantly shorter overall survival time than those without (P [ .0481). Background: Thymic carcinoma is a rare mediastinal neoplasm, and little is known about its genetic variability, which has hampered the development of targeted therapies. Patients and Methods: We tested a next-generation sequencing panel containing 50 common cancer-related genes in 48 cases of thymic carcinoma and 6 cases of thymic neuroendocrine tumor. Results: We detected 42 variant calls in 21 of 54 cases. There was no significant difference in mutation frequency between thymic carcinoma and thymic neuroendocrine tumors. Among these, TP53 was the most frequently mutated gene (18.5%), followed by KIT (7.4%) and PDGFRA (5.6%). According to the gene pathways and groups, the p53 pathway, including TP53 and ATM, was most frequently affected (20.4%), followed by the receptor tyrosine kinase (RTK)/RAS pathway (18.5%) and PI3K pathway (5.6%). According to the OncoKB, an expert-guided precision oncology knowledge base, 7 genes among 10 cases (18.5%) were annotated with level 1 evidence, suggesting potentially therapeutic targets. Prognostic analyses, conducted in thymic squamous cell carcinomas, revealed that tumor cases harboring gene mutations in RTKs, including KIT (7.4%), PDGFRA (5.6%) and EGFR (3.7%), were significantly associated with a worse overall survival time (P = .0481). Among clinicopathologic factors, the advanced Masaoka stage was marginally associated with a worse overall survival (P = .0757). In the subsequent multivariate analysis, neither of the factors achieved statistical significance. Conclusions: In this preliminary next-generation sequencing study, we unexpectedly found evidence suggesting that several gene mutations might be therapeutic targets. The gene mutations in RTKs may be a valuable prognostic factor in thymic squamous

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