细胞癌 z-bo 2020-09-15 373

　　Exome sequencing is a genomic analysis method developed in recent years that uses sequence capture technology to capture and enrich the DNA of the exon region of the whole genome for high-throughput sequencing. It is an efficient strategy for selecting the coding sequence of the genome, and its cost is lower than that of genome sequencing. At present, exome sequencing has been successfully applied in the study of Mendelian diseases such as Miller syndrome, Kabuki syndrome, and severe craniocerebral malformations. There are also some other cancers and complex diseases that also use exome sequencing to observe highly correlated mutations.

　　In this new article, researchers from the Chinese Academy of Medical Sciences performed exome sequencing on 113 pairs of tumors and normal samples and 8 cell lines. Each tumor generated an average of 82 non-silent mutations. . They confirmed that the mutation spectrum of esophageal squamous cell carcinoma is very similar to that of other tissues, but different from that of esophageal adenocarcinoma.

　　Some genes related to cell cycle and apoptosis regulation have somatic mutations in 99% of cases, including TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 ( 9%) Gene. Some histone modifying genes, including KMT2D (also known as MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%), are frequently mutated. EP300 mutations are associated with poor survival prognosis. FAT1, FAT2, FAT3, or FAT4 mutations (27%) and AJUBA mutations (JUB; 7%) caused dysregulation of the Hippo signaling pathway, while NOTCH1, NOTCH2, or NOTCH3 mutations (22%) and FBXW7 mutations (5%) disrupted Notch signal path.

　　These findings describe the mutational landscape of esophageal squamous cell carcinoma in detail, indicating that mutations of some epigenetic regulatory factors may have potential prognostic and therapeutic significance.