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

Autor: Kiwerska K; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland. katarzyna.kiwerska@igcz.poznan.pl.; Department of Tumor Pathology, Greater Poland Cancer Center, Garbary 15, 61-866, Poznań, Poland. katarzyna.kiwerska@igcz.poznan.pl., Szaumkessel M; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland., Paczkowska J; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland., Bodnar M; Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Curie-Sklodowskiej 9, 85-094, Bydgoszcz, Poland.; Department of Otolaryngology and Laryngeal Oncology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland., Byzia E; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland., Kowal E; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland., Kostrzewska-Poczekaj M; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland., Janiszewska J; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland., Bednarek K; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland., Jarmuż-Szymczak M; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland.; Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Szamarzewskiego 82/84, 60-569, Poznań, Poland., Kalinowicz E; Department of Otolaryngology and Laryngeal Oncology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland., Wierzbicka M; Department of Otolaryngology and Laryngeal Oncology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland., Grenman R; Department of Otorhinolaryngology, Head and Neck Surgery and Department of Medical Biochemistry, Turku University Central Hospital and Turku University, PO Box 52 FI-20521, Turku, Finland., Szyfter K; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland.; Department of Audiology and Phoniatrics, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland., Marszałek A; Oncologic Pathology and Prophylaxis Poznan University of Medical Sciences & Greater Poland Cancer Center, Garbary 15, 61-866, Poznań, Poland., Giefing M; Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479, Poznań, Poland.; Department of Otolaryngology and Laryngeal Oncology, Poznan University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznań, Poland.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Jul 14; Vol. 7 (1), pp. 5386. Date of Electronic Publication: 2017 Jul 14.
DOI: 10.1038/s41598-017-05857-1
Abstrakt: 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 < 0.0001) and in 15/21 primary tumors (p < 0.0001)) prevails in the gene transcriptional loss. As a proof of principle, we show that Decitabine - a hypomethylating agent - restores 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.
Databáze: MEDLINE
Externí odkaz: