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1. Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors

Author

Katarzyna Kiwerska, Marcin Szaumkessel, Julia Paczkowska, Magdalena Bodnar, Ewa Byzia, Ewelina Kowal, Magdalena Kostrzewska-Poczekaj, Joanna Janiszewska, Kinga Bednarek, Małgorzata Jarmuż-Szymczak, Ewelina Kalinowicz, Małgorzata Wierzbicka, Reidar Grenman, Krzysztof Szyfter, Andrzej Marszałek, and Maciej Giefing

Subjects
Medicine, Science
Abstract

Abstract Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array). By RT-PCR we have confirmed complete FAM107A downregulation in laryngeal cancer cell lines (15/15) and primary tumors (21/21) and this finding was further supported by FAM107A protein immunohistochemistry (15/15). We further demonstrate that a combined two hit mechanism including loss of 3p and hypermethylation of FAM107A promoter region (in 9/15 cell lines (p

Published
2017
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2. Combined deletion and DNA methylation result in silencing of FAM107A gene in laryngeal tumors

Author

Marcin Szaumkessel, Malgorzata Jarmuz-Szymczak, Julia Paczkowska, Magdalena Kostrzewska-Poczekaj, Katarzyna Kiwerska, Magdalena Bodnar, Ewelina Kowal, Ewelina Kalinowicz, Reidar Grénman, Małgorzata Wierzbicka, Kinga Bednarek, Maciej Giefing, Andrzej Marszałek, Krzysztof Szyfter, Ewa Byzia, and Joanna Janiszewska

Subjects
0301 basic medicine, Antimetabolites, Antineoplastic, Science, Decitabine, Biology, Methylation, Article, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, medicine, Humans, Gene silencing, Genes, Tumor Suppressor, Phosphorylation, Promoter Regions, Genetic, Laryngeal Neoplasms, Gene, Neoplasm Staging, Multidisciplinary, Gene Expression Profiling, Nuclear Proteins, Cancer, Promoter, Microarray Analysis, medicine.disease, Molecular biology, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Hypomethylating agent, 030220 oncology & carcinogenesis, DNA methylation, Carcinoma, Squamous Cell, Immunohistochemistry, Medicine, Protein Processing, Post-Translational, medicine.drug
Abstract

Larynx squamous cell carcinoma (LSCC) is characterized by complex genotypes, with numerous abnormalities in various genes. Despite the progress in diagnosis and treatment of this disease, 5-year survival rates remain unsatisfactory. Therefore, the extended studies are conducted, with the aim to find genes, potentially implicated in this cancer. In this study, we focus on the FAM107A (3p14.3) gene, since we found its significantly reduced expression in LSCC by microarray profiling (Affymetrix U133 Plus 2.0 array). By RT-PCR we have confirmed complete FAM107A downregulation in laryngeal cancer cell lines (15/15) and primary tumors (21/21) and this finding was further supported by FAM107A protein immunohistochemistry (15/15). We further demonstrate that a combined two hit mechanism including loss of 3p and hypermethylation of FAM107A promoter region (in 9/15 cell lines (p p FAM107A expression (5 to 6 fold increase) in the UT-SCC-29 cell line, characterized by high DNA methylation. Therefore, we report the recurrent inactivation of FAM107A in LSCC, what may suggest that the gene is a promising tumor suppressor candidate involved in LSCC development.

Published
2017

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