Mutations, Differential Gene Expression, and Chimeric Transcripts in Esophageal Squamous Cell Carcinoma Show High Heterogeneity
| Autor: | Nathalia Meireles Da Costa, Carolina Furtado, Miguel A. M. Moreira, Mariana Boroni, Hector N. Seuanez, Paulo Thiago de Souza-Santos, Albert N. Menezes, Tatiana de Almeida Simão, Luis Felipe Ribeiro Pinto, Pedro Nicolau-Neto, Sheila Coelho Soares Lima, Lilian Brewer |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Original article business.industry medicine.medical_treatment Wnt signaling pathway Biology lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Esophageal squamous cell carcinoma lcsh:RC254-282 Targeted therapy 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Text mining Oncology 030220 oncology & carcinogenesis Gene expression Genomic Profile medicine Cancer research business Gene Synteny |
| Zdroj: | Translational Oncology Translational Oncology, Vol 11, Iss 6, Pp 1283-1291 (2018) |
| ISSN: | 1936-5233 |
| Popis: | Esophageal squamous cell carcinoma (ESCC) is a frequent and lethal neoplasia. As recent advances in targeted therapy have not improved ESCC prognosis, characterization of molecular alterations associated to this tumor is of foremost relevance. In this study, we analyze, for the first time, the complete genomic profile of ESCC by RNA-seq. TP53 was the most frequently mutated gene in the investigation and validation sets (78.6% and 67.4%, respectively). Differential expression analysis between tumor and nontumor adjacent mucosa showed 6698 differentially expressed genes, most of which were overexpressed (74%). Enrichment analysis identified overrepresentation of Wnt pathway, with overexpressed activators and underexpressed inactivators, suggesting activation of canonical and noncanonical Wnt signaling pathways. Higher WNT7B expression was associated with poor prognosis. Twenty-one gene fusions were identified in 50% of tumors, none of which involving the same genes in different patients; 71% of fusions involved syntenic genes. Comparisons with TCGA data showed co-amplification of seven gene pairs involved in fusions in the present study (~33%), suggesting that these rearrangements might have been driven by chromoanagenesis. In conclusion, genomic alterations in ESCC are highly heterogeneous, impacting negatively in target therapy development. |
| Databáze: | OpenAIRE |
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