Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas  

作　　者：Jianwei Zhang Hanxiao Chen Junli Zhang Sha Wang Yanfang Guan Wenguang Gu Jie Li Xiaotian Zhang Jian Li Xicheng Wang Zhihao Lu Jun Zhou Zhi Peng Yu Sun Yang Shao Lin Shen Minglei Zhuo Ming Lu 

机构地区：[1]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Gastrointestinal Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China [2]Department of Radiation Therapy,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen 518172,China [3]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department I of Thoracic Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China [4]Medical Department,Nanjing Geneseeq Technology Inc.,Nanjing 210061,China [5]Geneplus-Beijing,Beijing 102200,China [6]State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Beijing Key Laboratory of Carcinogenesis and Translational Research,Department of Gastrointestinal Oncology,Peking University Cancer Hospital&Institute,Beijing 100142,China [7]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Pathology,Peking University Cancer Hospital&Institute,Beijing 100142,China

出　　处：《Chinese Journal of Cancer Research》2024年第1期90-102,共13页中国癌症研究（英文版）

基　　金：supported by the Major Program of National Natural Science Foundation of China (No. 91959205);National Natural Science Foundation of China (No. 82141117);The Capital’s Funds for Health Improvement and Research (CFH) (No. 2022-2-1023);Beijing Xisike Clinical Oncology Research Foundation Ypierrefabre (No. 202101-0099);Beijing Municipal Administration of Hospitals Incubating Program (No. PX2020045);Science Foundation of Peking University Cancer Hospital (No. 2020-4)。

摘　　要：Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its counterpart.Methods: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable genes.Results: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive adenocarcinomas.Among the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

关 键 词：Neuroendocrine carcinoma gastroenteropancreatic LUNG genetic alterations molecular markers 

分 类 号：R735[医药卫生—肿瘤]