Abstract
BackgroundEsophageal sarcomatoid carcinoma (ESC) is a rare disease with a mixture of both carcinomatous and sarcomatous components in the tumor. Its genetic background and mechanisms of oncogenesis remain largely unknown.MethodsHere we performed targeted next generation sequencing (NGS) on a pan-cancer gene panel in 15 ESC tumors to explore their genetic alterations, and aimed to identify clinically actionable mutations for future treatment instructions.ResultsTP53 alterations were identified in all patients. Alterations in receptor tyrosine kinases (RTK) were identified in 10 out of 15 patients. Members of downstream RAS and PI3-kinase pathways are also mutated in 10 patients, and PIK3CA is the top mutated gene in these pathways. In addition, we identified mutations on histone modification genes in 5 patients, including histone acetyltransferase gene EP300 and its homologue CREBBP, lysine methyltransferase genes KMT2A and KMT2B, and lysine demethylase gene KDM5A. Finally, mismatch repair (MMR) genes and proofreading gene POLE all together were mutated in one third of the ESC patients.ConclusionsThis is the first study to unravel the mutational profile of ESC tumors. Our findings could match 9 patients to the targeted therapies currently available in clinical practice or in active clinical trials, suggesting the potential utility of targeted therapies for this rare disease in the future.
Highlights
Esophageal sarcomatoid carcinoma (ESC) is a rare disease with a mixture of both carcinomatous and sarcomatous components in the tumor
Molecular pathways that were influenced by identified mutations Of these 15 patients, a total of 161 genetic alterations were identified in 94 genes (Additional file 2: Table S2)
Both proteins encoded by EP300 and CREBBP are suggested as tumor suppressors and indicative of poor prognosis in esophageal squamous cell carcinoma (ESCC) [11]
Summary
Esophageal sarcomatoid carcinoma (ESC) is a rare disease with a mixture of both carcinomatous and sarcomatous components in the tumor. Esophageal sarcomatoid carcinoma (ESC) is a rare malignant tumor with a reported incidence of below 2% in esophageal carcinomas [1, 2]. Surgery to dissect tumors and nearby lymph nodes, complemented with adjuvant chemotherapy and/ or radiotherapy before or afterwards, is the most adoptive treatment to this disease, and targeted therapies still remain unavailable. The 3-year survival rate of ESC is close to 60%, which is much higher than that of esophageal squamous cell carcinoma (ESCC) [6, 7]. Its 5year survival rate is close to that of ESCC, likely due to a lack of effective treatments to recurrent diseases
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