부산대학교 도서관

Simple Summary: The majority of patients with sinonasal intestinal-type adenocarcinoma are wood and leather workers. However, the genetic changes that lead to these tumors are not well known. We analyzed 50 tumors for mutations in a set of 120 genes that may be involved in causing this cancer type. We found that 72% of cases carried mutations in genes that are active in Wnt, DNA damage response, MAPK or PI3K signaling pathways. Pathway activation was not related to mutations of genes in these pathways, except for nuclear β-catenin expression to Wnt pathway mutation. No specific gene mutation, mutated pathway, nor pathway activity level was associated with histological subtype, clinical data or survival. Finally, none of the identified mutated genes occurred in such frequency as to be considered a characteristic genetic feature of sinonasal intestinal-type adenocarcinoma. Sinonasal intestinal-type adenocarcinoma (ITAC) is strongly related to occupational exposure to wood and leather dust, however, little is known on the genetic alterations involved in tumor development and progression. The aim of this study was to identify tumorigenic signaling pathways affected by gene mutations and their relation to clinical features. We applied whole exome sequencing of 120 cancer-related genes in 50 ITACs and analyzed the signaling activity of four specific pathways frequently affected by mutations. Genes involved in DNA damage response showed somatic mutations in 30% of cases, including four tumors that also harbored germline mutations. Genes in Wnt, MAPK and PI3K pathways harbored mutations in 20%, 20% and 24% of cases, respectively. Mutations and copy number gains in receptor tyrosine kinases possibly affecting MAPK and PI3K pathways occurred in 44% of cases. Expression of key pathway proteins showed no correlation to mutations in these pathways, except for nuclear β-catenin and APC/CTNNB1 mutation. No specific gene mutation, mutated pathway, nor pathway activity level showed correlation to clinical data or survival. In addition, a similar mutational profile was observed among histological subtypes. The wide spectrum of gene mutations suggests that ITAC is a genetically heterogeneous without specific characterizing gene mutations. [ABSTRACT FROM AUTHOR]