Abstract 1707: Enteric-type adenocarcinoma in head and neck: Dissecting oncogenic genes alterations through whole transcriptome analysis

Abstract

Abstract IntroductionAdenocarcinomas of nose/paranasal are uncommon tumors; an important one is that which shows enteric differentiation (ETA). ETA is typically seen in adults, many whom have had occupational exposure (mainly wood and leather). The histogenesis of ETA is uncertain, an origin from transdifferentiation of the respiratory epithelium is a possibility. We previously reported evidence for such transformation in similar tumors at other anatomic locations (Eustachian tube, base of tongue, epiglottis). Due to the rarity of these tumors, their molecular profile is not well known. To investigate the molecular profile and identify potential oncogenic drivers we compared the whole transcriptome of ETA at different anatomic location in head and neck. Materials and Methods10 adenocarcinomas of head and neck formed the material of this study. These samples along with matching normal mucosa were microdisected from FFPE. Pools of RNA were subjected to expression profiling using whole-transcriptome shotgun sequencing. Results 20 tumors were divided as follows: 10 sinonasal and 10 non-sinonasal adenocarcinomas. The sinonasal adenocarcinomas were classified as 8 ETA and 2 seromucinous type (non-ETA, nasal). The 10 non-sinonasal HN adenocarcinomas divided according to histologies and location: 4 ETA (BOT/mobile-2, submandibular-1, ear-1); 3 mucinous adenocarcinoma (buccal-2; 1 ectopic rests neck L2); 1 adenoid cystic carcinoma of BOT; 1 polymorphous adenocarcinoma of buccal; one larynx metastatic colonic adenocarcinoma. Differential gene expression profiles from adenocarcinomas versus normal mucosa were generated and compared to each other. Comparing all tumors versus all normal mucosal tissues, 3029 genes and noncoding transcripts were detected as differentially expressed with fold change >2 and p-values< 0.05 (1625 upregulated and 1404 downregulated genes). These genes and transcripts were annotated and analyzed using IPA program. Further refined analysis of ETA at sinonasal locations showed 622 specific/ non-overlapping genes (325 upregulated and 297 downregulated). The ETA group at other anatomic location segregated with 3344 specific differentially expressed genes, mostly upregulated (1887 versus 1457 downregulated genes). The highest expressed genes and potential drivers were predominantly development- and differentiation-related genes. ConclusionWe assume that ETA are mainly defined by overexpressed developmental homeobox genes, which provide the potential for transformation/ plasticity, along with the differentiation and proliferation behavior of neoplastic cells. The data form the basis for understanding cell fate determination and cellular homeostasis in the normal respiratory mucosa at different anatomic sites, and the contribution of different mucosal components to the etiology/ molecular pathology of ETA. Citation Format: Diana Bell, Achim H. Bell, Ehab Y. Hanna. Enteric-type adenocarcinoma in head and neck: Dissecting oncogenic genes alterations through whole transcriptome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1707.