Tadashi Sakane1, Yuma Sakamoto2, Ayako Masaki2, Takayuki Murase2, Katsuhiro Okuda3, Ryoichi Nakanishi3, Hiroshi Inagaki4. 1. Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 2. Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 3. Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. 4. Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. Electronic address: hinagaki@med.nagoya-cu.ac.jp.
Abstract
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.
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.
Authors: Stefan Küffer; Jessica Grabowski; Satoru Okada; Nikolai Sojka; Stefan Welter; Alexander von Hammerstein-Equord; Marc Hinterthaner; Lucia Cordes; Xenia von Hahn; Denise Müller; Christian Sauer; Hanibal Bohnenberger; Alexander Marx; Philipp Ströbel Journal: Cancers (Basel) Date: 2022-09-29 Impact factor: 6.575