PMID- 29566279 OWN - NLM STAT- MEDLINE DCOM- 20190304 LR - 20211204 IS - 1098-2744 (Electronic) IS - 0899-1987 (Linking) VI - 57 IP - 7 DP - 2018 Jul TI - Recurrent transcriptional loss of the PCDH17 tumor suppressor in laryngeal squamous cell carcinoma is partially mediated by aberrant promoter DNA methylation. PG - 878-885 LID - 10.1002/mc.22808 [doi] AB - Protocadherins are cell-cell adhesion molecules encoded by a large family of genes. Recent reports demonstrate recurrent silencing of protocadherin genes in tumors and provide strong arguments for their tumor supresor functionality. Loss of protocadherins may contribute to cancer development not only by altering cell-cell adhesion, that is a hallmark of cancer, but also by enhancing proliferation and epithelial mesenchymal transition of cells via deregulation of the WNT signaling pathway. In this study we have further corroborated our previous findings on the involvement of PCDH17 in laryngeal squamous cell carcinoma (LSCC). We used bisulfite pyrosequencing to analyze a cohort of primary LSCC tumors for alterations in PCDH17 promoter DNA methylation as an alternative gene inactivation mechanism to the homozygous deletions reported earlier. Moreover, we analyzed primary LSCC samples by immunohistochemistry for PCDH17 protein loss. We identified recurrent elevation of PCDH17 promoter DNA methylation in 32/81 (40%) primary tumors (P < 0.001) and therein hypermethylation of 12 (15%) cases in contrast to no tumor controls (n = 24) that were all unmethylated. Importantly, DNA demethylation by decitabine has restored low level PCDH17 expression in LSCC cell lines. In conclusion, we provide a mechanistic explanation of recurrently observed PCDH17 silencing in LSCC by demonstrating the role of promoter methylation in this process. In light of these findings and recent reports showing that PCDH17 methylation is detectable in serum of cancer patients we suggest that testing PCDH17 DNA methylation might serve as a potential biomarker in LSCC. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Byzia, Ewa AU - Byzia E AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Soloch, Natalia AU - Soloch N AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Bodnar, Magdalena AU - Bodnar M AD - Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland. AD - Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Szaumkessel, Marcin AU - Szaumkessel M AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Kiwerska, Katarzyna AU - Kiwerska K AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. AD - Department of Tumor Pathology, Greater Poland Cancer Center, Poznan, Poland. FAU - Kostrzewska-Poczekaj, Magdalena AU - Kostrzewska-Poczekaj M AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Jarmuz-Szymczak, Malgorzata AU - Jarmuz-Szymczak M AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. AD - Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland. FAU - Szylberg, Lukasz AU - Szylberg L AD - Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland. FAU - Wierzbicka, Malgorzata AU - Wierzbicka M AD - Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Bartochowska, Anna AU - Bartochowska A AD - Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Kalinowicz, Ewelina AU - Kalinowicz E AD - Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Grenman, Reidar AU - Grenman R AD - Department of Otorhinolaryngology, -Head and Neck Surgery, Turku University Central Hospital and Turku University, Turku, Finland. AD - Department of Medical Biochemistry, Turku University Central Hospital and Turku University, Turku, Finland. FAU - Szyfter, Krzysztof AU - Szyfter K AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. FAU - Marszalek, Andrzej AU - Marszalek A AD - Department of Tumor Pathology and Prophylaxis, Poznan University of Medical Sciences and Greater Poland Cancer Center, Poznan, Poland. FAU - Giefing, Maciej AU - Giefing M AUID- ORCID: 0000-0002-4760-8246 AD - Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. AD - Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180406 PL - United States TA - Mol Carcinog JT - Molecular carcinogenesis JID - 8811105 RN - 0 (Cadherins) RN - 0 (PCDH17 protein, human) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cadherins/*genetics MH - Carcinoma, Squamous Cell/*genetics MH - Cell Line, Tumor MH - DNA Methylation/*genetics MH - Female MH - Humans MH - Laryngeal Neoplasms/*genetics MH - Male MH - Middle Aged MH - Promoter Regions, Genetic/genetics MH - Transcription, Genetic/*genetics MH - Tumor Suppressor Proteins/*genetics MH - Wnt Signaling Pathway/genetics OTO - NOTNLM OT - bisulfite pyrosequencing OT - epigenetics OT - head and neck cancer OT - protocadherins EDAT- 2018/03/23 06:00 MHDA- 2019/03/05 06:00 CRDT- 2018/03/23 06:00 PHST- 2017/11/30 00:00 [received] PHST- 2018/03/06 00:00 [revised] PHST- 2018/03/20 00:00 [accepted] PHST- 2018/03/23 06:00 [pubmed] PHST- 2019/03/05 06:00 [medline] PHST- 2018/03/23 06:00 [entrez] AID - 10.1002/mc.22808 [doi] PST - ppublish SO - Mol Carcinog. 2018 Jul;57(7):878-885. doi: 10.1002/mc.22808. Epub 2018 Apr 6.