PMID- 34269310 OWN - NLM STAT- In-Process VI - 17 IP - 3 TI - Multiregion sequencing and subclonal analysis reveal intratumoral heterogeneity in esophageal squamous cell carcinoma. PG - 756-763 LA - eng PT - Journal Article PL - India TA - J Cancer Res Ther JT - Journal of cancer research and therapeutics JID - 101249598 IS - 1998-4138 (Electronic) LID - 10.4103/jcrt.jcrt_270_21 [doi] FAU - Gao, Dongni AU - Gao D AD - Department of Clinical Medicine, Cheeloo College of Medicine, Shandong University; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. FAU - Zhang, Zicheng AU - Zhang Z AD - Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong; Department of Radiation Oncology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China. FAU - Yang, Qiwei AU - Yang Q AD - Department of Clinical Medicine, Cheeloo College of Medicine, Shandong University; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. FAU - Li, Baosheng AU - Li B AD - Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China. IS - 1998-4138 (Linking) SB - IM OTO - NOTNLM OT - Esophageal squamous cell carcinoma OT - intratumoral heterogeneity OT - tumor evolution LR - 20210716 DP - 2021 Jul AB - Purpose: The aim of this study was to investigate intratumoral genomic heterogeneity and subclonal structure of esophageal squamous cell carcinoma (ESCC). Materials and Methods: Multiregion whole-exome sequencing was performed on 24 surgically acquired tumor samples from five untreated ESCC patients collected in 2019 to determine the heterogeneity of mutational landscape within tumors. Phylogenetic analysis and mutation process analysis were used to explore the distribution and dynamic changes of mutation spectrum, and subclone analysis was used to explore the subclonal composition and spatial structure of ESCC. Results: An average of 60.2% of mutations were found heterogenous. TP53 and NOTCH1 mutations were confirmed to be early events, and mutations unique in different tumor regions showed a pattern of branching evolution. A large proportion of mutations were associated with abnormal activity of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family, and significant differences in mutation types between trunk and branch variants were found. Subclonal structure exhibited spatial correspondence and spatial limitations, and different genomic features were characterized between close and distant clones. Conclusions: There is significant intratumoral genomic heterogeneity in the five ESCCs, and their subclonal structure is related to spatial locations.