TY - JOUR T1 - Molecular Characterization of Sinonasal Undifferentiated Carcinoma—Past, Present, and Future AU - Takahashi, Yoko AU - Hanna, Ehab Y. PY - 2023 DA - August DO - 10.5152/ejra.2023.23092 JF - European Journal of Rhinology and Allergy JO - Eur J Rhinol Allergy PB - Turkish Rhinology Society WT - DergiPark SN - 2636-8072 SP - 37 EP - 41 VL - 6 IS - 2 LA - en AB - Sinonasal undifferentiated carcinoma is a rare and aggressive tumor. Despite aggressive management of patients, their prognosis is still poor. To better understand the biological features of sinonasal undifferentiated carcinoma and develop reliable therapeutic strategies for this disease, molecular characterization of sinonasal undifferentiated carcinoma is crucial. However, even nearly a decade ago, sinonasal undifferentiated carcinoma was still a poorly understood malignancy on both the clinical and molecular levels. The advent of next-generation sequencing technologies has resulted in a significant increase in the identification of molecular markers, including diagnostic and predictive markers, as well as gene alterations, leading to emerging distinct entities and new therapeutic approaches for sinonasal undifferentiated carcinoma. As new technologies continue to develop, new molecular markers for sinonasal undifferentiated carcinoma are expected to be discovered. Nevertheless, regardless of the methodology employed, sample size remains a crucial factor for the success of such investigations. Therefore, it is essential to establish a centralized banking system through multi-institutional collaboration. Additionally, investigation of the tumor microenvironment, including spatial immunophenotyping, is necessary to develop successful immunotherapy approaches. KW - Sinonasal undifferentiated carcinoma KW - next-generation sequencing KW - molecular profiling KW - gene expression KW - DNA mutations KW - DNA methylation CR - Chambers KJ, Lehmann AE, Remenschneider A, et al. Incidence and survival patterns of sinonasal undifferentiated carcinoma in the United States. J Neurol Surg B Skull Base. 2015;76(2):94-100. CR - Frierson HF, Jr, Mills SE, Fechner RE, Taxy JB, Levine PA. Sinonasal undifferentiated carcinoma. An aggressive neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma. Am J Surg Pathol. 1986; 10(11):771-779. CR - Justin A, Bishop LDRT, Loney EL. Nasal, Paranasal, and Skull Base Tumors. WHO Classification of Tumours Editorial Board Head and Neck Tumours. 5th ed. Lyon, France: International Agency for Research on Cancer; 2022. Abdelmeguid AS, Bell D, Hanna EY. Neuroendocrine carcinoma and sinonasal undifferentiated carcinoma. Adv Otorhinolaryngol. 2020;84:168-184. CR - Bell D, Hanna EY, Weber RS, et al. Neuroendocrine neoplasms of the sinonasal region. Head Neck. 2016;38(suppl 1):E2259-E2266. CR - Singh L, Ranjan R, Arava S, Singh MK. Role of p40 and cytokeratin 5/6 in the differential diagnosis of sinonasal undifferentiated carcinoma. Ann Diagn Pathol. 2014;18(5):261-265. CR - Wadsworth B, Bumpous JM, Martin AW, Nowacki MR, Jenson AB, Farghaly H. Expression of p16 in sinonasal undifferentiated carcinoma (SNUC) without associated human papillomavirus (HPV). Head Neck Pathol. 2011;5(4):349-354. CR - Gray ST, Herr MW, Sethi RK, et al. Treatment outcomes and prognostic factors, including human papillomavirus, for sinonasal undifferentiated carcinoma: a retrospective review. Head Neck. 2015;37(3):366-374. CR - Gollin SM, Janecka IP. Cytogenetics of cranial base tumors. J Neurooncol. 1994;20(3):241-254. CR - Gil Z, Orr-Urtreger A, Voskoboinik N, et al. Cytogenetic analysis of sinonasal carcinomas. Otolaryngol Head Neck Surg. 2006;134(4):654-660. CR - Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature. 2001;411(6835):355-365. CR - Chernock RD, Perry A, Pfeifer JD, Holden JA, Lewis JS, Jr. Receptor tyrosine kinases in sinonasal undifferentiated carcinomas--evaluation for EGFR, c-KIT, and HER2/neu expression. Head Neck. 2009;31(7):919-927. CR - MacConaill LE, Campbell CD, Kehoe SM, et al. Profiling critical cancer gene mutations in clinical tumor samples. PLoS One. 2009;4(11):e7887. CR - Gelbard A, Hale KS, Takahashi Y, et al. Molecular profiling of sinonasal undifferentiated carcinoma. Head Neck. 2014;36(1):15-21. CR - Awata T, Inoue K, Kurihara S, et al. A common polymorphism in the 5′-untranslated region of the VEGF gene is associated with diabetic retinopathy in type 2 diabetes. Diabetes. 2002;51(5):1635-1639. CR - Koukourakis MI, Papazoglou D, Giatromanolaki A, Bougioukas G, Maltezos E, Sivridis E. VEGF gene sequence variation defines VEGF gene expression status and angiogenic activity in non-small cell lung cancer. Lung Cancer. 2004;46(3):293-298. CR - Lee SJ, Lee SY, Jeon HS, et al. Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(3):571-575. CR - McCarron SL, Edwards S, Evans PR, et al. Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res. 2002;62(12): 3369-3372. CR - Takahashi Y, Kupferman ME, Bell D, et al. Establishment and characterization of novel cell lines from sinonasal undifferentiated carcinoma. Clin Cancer Res. 2012;18(22):6178-6187. CR - Stirnweiss A, Oommen J, Kotecha RS, Kees UR, Beesley AH. Molecular-genetic profiling and high-throughput in vitro drug screening in NUT midline carcinoma-an aggressive and fatal disease. Oncotarget. 2017;8(68):112313-112329. CR - Takahashi Y, Lee J, Pickering C, et al. Human epidermal growth factor receptor 2/neu as a novel therapeutic target in sinonasal undifferentiated carcinoma. Head Neck. 2016;38(suppl 1):E1926-E1934. CR - Takahashi Y, Gleber-Netto FO, Bell D, et al. Identification of novel diagnostic markers for sinonasal undifferentiated carcinoma. Head Neck. 2019;41(8):2688-2695. CR - Amit M, Abdelmeguid AS, Watcherporn T, et al. Induction chemotherapy response as a guide for treatment optimization in sinonasal undifferentiated carcinoma. J Clin Oncol. 2019;37(6):504-512. CR - Takahashi Y, Gleber-Netto FO, Bell D, et al. Identification of markers predictive for response to induction chemotherapy in patients with sinonasal undifferentiated carcinoma. Oral Oncol. 2019;97:56-61. CR - Geman D, d'Avignon C, Naiman DQ, Winslow RL. Classifying gene expression profiles from pairwise mRNA comparisons. Stat Appl Genet Mol Biol. 2004;3:Article19. CR - Jo VY, Chau NG, Hornick JL, Krane JF, Sholl LM. Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma. Mod Pathol. 2017;30(5):650-659. CR - Dogan S, Chute DJ, Xu B, et al. Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. J Pathol. 2017;242(4):400-408. CR - Dogan S, Frosina D, Fayad M, et al. The role of a monoclonal antibody 11C8B1 as a diagnostic marker of IDH2-mutated sinonasal undifferentiated carcinoma. Mod Pathol. 2019;32(2):205-215. CR - Mito JK, Bishop JA, Sadow PM, et al. Immunohistochemical detection and molecular characterization of IDH-mutant sinonasal undifferentiated carcinomas. Am J Surg Pathol. 2018;42(8):1067-1075. CR - Riobello C, López-Hernández A, Cabal VN, et al. IDH2 mutation analysis in undifferentiated and poorly differentiated sinonasal carcinomas for diagnosis and clinical management. Am J Surg Pathol. 2020;44(3):396-405. CR - Yang H, Ye D, Guan KL, Xiong Y. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res. 2012;18(20):5562-5571. CR - Stein EM, DiNardo CD, Fathi AT, et al. Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib. Blood. 2019;133(7):676-687. CR - Agaimy A, Koch M, Lell M, et al. SMARC B1(IN I1)-d efici ent sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms. Am J Surg Pathol. 2014;38(9):1274-1281. CR - Bishop JA, Antonescu CR, Westra WH. SMARCB1 (INI-1)-deficient carcinomas of the sinonasal tract. Am J Surg Pathol. 2014;38(9):1282-1289. CR - James S, Lewis JAB, Gillison M, Westra WH, Yarbrough WG. Tumors of the nasal cavity, paranasal sinuses and skull base-sinonasal undifferentiated carcinoma. In: Adel K., El-Naggar JKCC, Grandis J. R., Takata T., Slootweg P. J., eds. WHO Classification of Head and Neck Tumors. 4th ed. Lyon: International Agency for Research on Cancer; 2017:18-20. CR - Centore RC, Sandoval GJ, Soares LMM, Kadoch C, Chan HM. Mammalian SWI/SNF chromatin remodeling complexes: emerging mechanisms and therapeutic strategies. Trends Genet. 2020;36(12):936-950. CR - Agaimy A, Hartmann A, Antonescu CR, et al. SMARCB1 (INI-1)-deficient­ sinonasal carcinoma: a series of 39 cases expanding the morphologic and clinicopathologic spectrum of a recently described entity. Am J Surg Pathol. 2017;41(4):458-471. CR - Chitguppi C, Rabinowitz MR, Johnson J, et al. Loss of SMARCB1 expression confers poor prognosis to sinonasal undifferentiated carcinoma. J Neurol Surg B Skull Base. 2020;81(6):610-619. CR - Kalimuthu SN, Chetty R. Gene of the month: SMARCB1. J Clin Pathol. 2016;69(6):484-489. CR - Lee VH, Tsang RK, Lo AWI, et al. SMARCB1 (INI-1)-deficient sinonasal carcinoma: a systematic review and pooled analysis of treatment outcomes. Cancers (Basel). 2022;14(13). CR - Agaimy A, Weichert W. SMARCA4-deficient sinonasal carcinoma. Head Neck Pathol. 2017;11(4):541-545. CR - Jurmeister P, Glöß S, Roller R, et al. DNA methylation-based classification of sinonasal tumors. Nat Commun. 2022;13(1):7148. CR - Dogan S, Vasudevaraja V, Xu B, et al. DNA methylation-based classification of sinonasal undifferentiated carcinoma. Mod Pathol. 2019;32(10):1447-1459. CR - Lokk K, Modhukur V, Rajashekar B, et al. DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns. Genome Biol. 2014;15(4):r54. CR - Nishiyama A, Nakanishi M. Navigating the DNA methylation landscape of cancer. Trends Genet. 2021;37(11):1012-1027. CR - Ozgur Mete LDRT. Neuroendocrine Neoplasms and Paraganglioma. WHO Classification of Tumours Editorial Board Head and Neck Tumours. 5th ed. Lyon, France: International Agency for Research on Cancer; 2022. CR - Bell D, Bell A, Ferrarotto R, et al. High-grade sinonasal carcinomas and surveillance of differential expression in immune related transcriptome. Ann Diagn Pathol. 2020;49:151622. CR - Villanueva-Fernández E, Hermsen MA, Suárez-Fernández L, et al. Biomarkers for immunotherapy in poorly differentiated sinonasal tumors. Biomedicines. 2022;10(9). UR - https://doi.org/10.5152/ejra.2023.23092 L1 - https://dergipark.org.tr/en/download/article-file/5398622 ER -