Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi 1304-6187 Sağlık Bakanlığı Ankara Eğitim ve Araştırma Hastanesi 10.20492/aeahtd.880228 Clinical Sciences Klinik Tıp Bilimleri SİNONAZAL İNVERTED PAPİLLOMLU VAKALARDA KROMOZOMAL MİKROARRAY ANALİZİ CHROMOSOMAL MICROARRAY ANALYSIS OF CASES WITH SINONASAL INVERTED PAPILLOMA https://orcid.org/0000-0001-6226-4712 Çitli Şenol TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR. https://orcid.org/0000-0003-1840-6052 Erdim İbrahim TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ https://orcid.org/0000-0002-0346-8704 Sapmaz Emrah TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR. https://orcid.org/0000-0002-5356-2846 Somuk Battal Tahsin TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TIP PR. 04 30 2022 55 1 5 8 02 15 2021 09 13 2021 Copyright © 2003, Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi 2003 Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi

Amaç: Mikroarray yöntemiyle sinonazal inverted papillomlu (SNIP) hastalarda etiyolojiden sorumlu olabilecek olası genetik varyasyonları saptamak Gereç ve Yöntem: Üçüncü basamak bir hastanenin Kulak-Burun-Boğaz Anabilim dalı tarafından Ocak 2014 - Ocak 2019 yılları arasında SNIP nedeniyle opere edilmiş 16 kişi hastane kayıtlarından tespit edildi. Ulaşılabilinen ve herhangi bir konjenital sistemik hastalığı olmayıp çalışmaya katılmayı kabul eden 7 kişi çalışmaya alındı. Çalışmaya alınan vakalara Tıbbi Genetik Anabilim dalı tarafından kromozomal mikroarray analizi (KMA) uygulandı. Bulgular: KMA yaşları 29 ile 67 arasında değişen altı erkek ve bir bayan hastaya uygulandı. Vakalardan birinde (Vaka 7) hiç bir varyant saptanamazken diğer altı vakada benign varyantlar tespit edildi. Altı vakada ortak olarak 14q32.33 lokalizasyonundaki duplikasyon varyantı görüldü. Varyantların üçü (6p25.3, 7q11.21, 14q32.33) herhangi bir gen içermezken 22. kromozom üzerinde saptanan diğer iki varyasyonun gen içeriği mevcuttu. Bunlardan vaka1 ve vaka4 de saptanan 22q11.21 lokalizasyonundaki ortalama büyüklüğü 12 kilobaz (kb) olarak saptanan duplikasyon şeklindeki varyasyon Tbx1 genini içerirken sadece vaka 5’te saptanan 22q11.22 lokalizasyonundaki yaklaşık 150 kb büyüklüğe sahip varyasyon mir650 genini içermektedir. Çalışmada ayrıca delesyon şeklinde saptanan tek Copy Number Varyasyon (CNV) 6p25.3 lokalizasyonundaki gen içeriği olmayan yaklaşık 30 kb büyüklüğüdeki varyasyondu. Bunun dışında saptanan CNV’lerin hepsi duplikasyon şeklindeydi. Sonuç: Çalışmamızda SNIP’lu hastalarda benign varyasyonlar saptamakla beraber herhangi bir patojenik veya olası patojenik varyasyon saptanmamıştır.

Aim: To detect possible genetic variations in the etiology of sinonasal inverted papilloma (SNIP) by using microarray method Material and Method: Sixteen cases who had been operated for SNIP between January 2014 and January 2019 in Ear-Nose-Throat Clinic of a tertiary hospital were found from hospital recordings. Seven patients who had been reached by phone, accepted to take part in the study and didn’t have systemic congenital disease were included the study. Chromosomal microarray analysis (CMA) was applied to cases by Medical Genetic Clinic. Results: CMA was applied to 6 males and 1 female whose age varied between 29 and 67. Although no variation was detected in one case (Case 7), benign variations were detected in the other six cases. Duplication in 14q32.33 localization was met as a same variation in the 6 cases. Although three variations (6p25.3, 7q11.21, 14q32.33) didn’t have any genes, other two variations located in 22nd chromosome had gene content. While variation in case 1 and case 4 detected in 22q11.21 localization was a duplication as 12 kilobase (kb) size and contains Tbx1 gene, only case 5 had a 150 kb size variation detected in 22q11.22 localization and contains mir650 gene. Furthermore only one Copy Number Variation (CNV), approximately 30 kb size, was found as a deletion in 6p25.3 localization that didn’t have gene. All other CNVs were detected as duplication.Conclusion: Although benign variations were found in patients with SNIP, we couldn’t find pathogenic or possible pathogenic variations.

 Sinonazal inverted papilloma mikroarray analiz Sinonasal inverted papilloma microarray analysis 1. Batsakis JG, Suarez P. Schneiderian papillomas and carcinomas: a review. Adv Anat Patho. 2001; 18: 53–64. 2. Wang MJ, Noel JE. Etiology of sinonasal inverted papilloma: A narrative review. World J Otorhinolaryngol Head Neck Surg. 2017; 3: 54–58. 3. Comoglu S, Ozturk E, Enver N, et al. Inverted papilloma: A Comprehensive Clinical Analysis. J Ist Faculty Med. 2016; 79: 4. 4. Cukurova I. Our approach to sinonasal inverted papillomas. J Med Updates. 2012;2(2):58-62. 5. Kaya E, Pinarbasli MO, Ture N, et al. Surgical Treatment Results in Sinonasal Inverted Papillomatous. Osmangazi Journal Med. 2018; 40:31-8. 6. Nygren A, Kiss K, von Buchwald C, et al. Rate of recurrence and malignant transformation in 88 cases with inverted papilloma between 1998–2008. Acta Otolaryngol. 2016; 136: 333–6. 7. Bugter O, Monserez DA, van Zijl F, et al. Surgical management of inverted papilloma; a single-center analysis of 247 patients with long follow-up. J Otolaryngol Head Neck Surg. 2017; 46: 67. 8. Demir UL. Endonazal Endoskopik İnverted Papillom Cerrahisinde Uludağ Deneyimi. Uludağ Üniv Tıp Fak Derg. 2020; 46: 53-7. 9. Chiu AG, Jackman AH, Antunes MB, et al. Radiographic and histologic analysis of the bone underlying inverted papillomas. Laryngoscope. 2006; 116: 1617–20. 10. Hyams VJ. Papillomas of the nasal cavity and paranasal sinuses. A clinicopathological study of 315 cases. Ann Otol Rhinol Laryngol. 1971; 80: 192–206. 11. Bejjani BA, Saleki R, Ballif BC, et al. Use of targeted array-based CGH for the clinical diagnosis of chromosomal imbalance: is less more? Am J Med Genet A. 2005; 134: 259-67. 12. Kamath BM, Thiel BD, Gai X, et al. SNP array mapping of chromosome 20p deletions: genotypes, phenotypes, and copy number variation. Human mutat. 2009; 30: 371-8. 13. Oncel GZ, Huseyinoglu N, Ozlece HK. Analysis of vitamin D Receptor Polymorphisms in Turkish Patients with Obstructive Sleep Apnea Syndrome. Dicle Med J. 2019; 46: 771 – 780. 14. Wang MJ, Noel JE. Etiology of sinonasal inverted papilloma: A narrative review. World J Otorhinolaryngol Head Neck Surg. 2016; 3: 54-8. 15. Deitmer T, Wiener C. Is there an occupationaletiology of invertedpapilloma of thenoseandsinuses. ActaOtolaryngol (Stockh). 1996; 116: 762–5. 16. Wright CF, Fitzgerald TW, Jones WD, et al. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet. 2015; 385: 1305–14. 17. Kearney HM, Thorland EC, Brown KK, et al. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011; 13: 680-5. 18. Ozyilmaz B, Kirbiyik O, Koc A, et al. Experiences in microarray based evaluation of developmental disabilities and congenital anomalies. Clin Genet. 2017; 92: 372-9. 19. Koolen DA, Pfundt R, de Leeuw N, et al. Genomic microarrays in mental retardation: a practical workflow for diagnostic applications. Hum Mutat. 2009; 30: 283-92. 20. Chieffo C, Garvey N, Gong W, et al. Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene. Genomics. 1997; 43: 267-77. 21. Vitelli F, Viola A, Morishima M. TBX1 is required for inner ear morphogenesis. Hum Molec Genet. 2003; 12: 2041-8. 22. Zhang, X, Zhu W, Zhang J, et al. MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity. Biochem Biophys Res Commun. 2010; 395: 275-80.