PMC:4385186 / 1700-3897 JSONTXT

{"project":"2_test","denotations":[{"id":"25839328-23374478-2052555","span":{"begin":214,"end":215},"obj":"23374478"},{"id":"25839328-23374478-2052556","span":{"begin":264,"end":265},"obj":"23374478"},{"id":"25839328-23374478-2052557","span":{"begin":417,"end":418},"obj":"23374478"},{"id":"25839328-23374478-2052558","span":{"begin":565,"end":566},"obj":"23374478"},{"id":"25839328-13130116-2052559","span":{"begin":711,"end":712},"obj":"13130116"},{"id":"25839328-13130116-2052560","span":{"begin":842,"end":843},"obj":"13130116"},{"id":"25839328-24552141-2052561","span":{"begin":970,"end":971},"obj":"24552141"},{"id":"25839328-20016485-2052562","span":{"begin":1169,"end":1170},"obj":"20016485"},{"id":"25839328-20016488-2052562","span":{"begin":1169,"end":1170},"obj":"20016488"},{"id":"25839328-24670651-2052563","span":{"begin":1362,"end":1363},"obj":"24670651"},{"id":"25839328-24686850-2052563","span":{"begin":1362,"end":1363},"obj":"24686850"},{"id":"25839328-23688607-2052564","span":{"begin":1552,"end":1554},"obj":"23688607"},{"id":"25839328-24709955-2052564","span":{"begin":1552,"end":1554},"obj":"24709955"},{"id":"25839328-22126580-2052564","span":{"begin":1552,"end":1554},"obj":"22126580"}],"text":"Introduction\nEsophageal carcinoma (EC) is the eighth most common and the sixth most lethal cancer worldwide. It tends to have a very poor prognosis as a result of the limited clinical approaches for early diagnosis1—the 5-year survival rate ranges from 10% to 25%.1 Clinically, this heterogeneous disease is categorized into two subtypes: esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC).1 Approximately 70% of the worldwide cases of ESCC occur in China, where the highest incidences are in the Taihang Mountains of north-central China.1 The risk of developing ESCC in China has been linked to factors such as dietary habits (e.g., hot food and betelnut chewing) and family history.2 Alcohol abuse and tobacco consumption explain nearly 90% of ESCC cases in Western countries but represent minor factors in China.2\nThe processes of DNA damage and repair, which produce the somatic mutations in a cancer genome, leave a signature of mutation.3 Recent analyses of comprehensive mutational catalogs from a malignant melanoma and a lung cancer revealed the characteristic mutational patterns of UV light and tobacco carcinogens, respectively.4,5 Exome-wide investigations have characterized somatic point mutations in ESCC and identified the ESCC-associated genes ZNF750 (MIM 610226), FAT1 (MIM 600976), FAT2 (MIM 604269), and FAM135B,6,7 and point mutations in genes such as PLCE1 (MIM 608414), XPF (MIM 133520), ALDH2 (MIM 100650), and MTHFR (MIM 607093) show different signatures between smokers and non-smokers with ESCC.8–10 However, such studies have been limited to a few genes, and it is unclear how representative these findings are of mutational processes operative in ESCC across the whole genome. In this study, we performed whole-genome sequencing (WGS) of 14 and whole-exome sequencing (WES) of 90 ESCC tumors and adjacent normal tissue from individuals recruited from the Taihang Mountains of north-central China and combined our data with those of 88 previously reported samples to extract the mutational signatures that cause somatic mutations in ESCC and identify driver genes or pathways contributing to this highly fetal disease in Chinese individuals."}