Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins
Summary: Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregiona...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723005879 |
| _version_ | 1797809187270426624 |
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| author | Miao-Zhen Qiu Qingjian Chen Dan-Yang Zheng Qi Zhao Qi-Nian Wu Zhi-Wei Zhou Li-Qiong Yang Qiu-Yun Luo Yu-Ting Sun Ming-Yu Lai Sha-Sha Yuan Feng-Hua Wang Hui-Yan Luo Feng Wang Yu-Hong Li Hui-Zhong Zhang Rui-Hua Xu |
| author_facet | Miao-Zhen Qiu Qingjian Chen Dan-Yang Zheng Qi Zhao Qi-Nian Wu Zhi-Wei Zhou Li-Qiong Yang Qiu-Yun Luo Yu-Ting Sun Ming-Yu Lai Sha-Sha Yuan Feng-Hua Wang Hui-Yan Luo Feng Wang Yu-Hong Li Hui-Zhong Zhang Rui-Hua Xu |
| author_sort | Miao-Zhen Qiu |
| collection | DOAJ |
| description | Summary: Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC. |
| first_indexed | 2024-03-13T06:48:46Z |
| format | Article |
| id | doaj.art-bf5aeca0e50d4f5bb3972a430c761164 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T06:48:46Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-bf5aeca0e50d4f5bb3972a430c7611642023-06-08T04:19:08ZengElsevierCell Reports2211-12472023-06-01426112576Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal originsMiao-Zhen Qiu0Qingjian Chen1Dan-Yang Zheng2Qi Zhao3Qi-Nian Wu4Zhi-Wei Zhou5Li-Qiong Yang6Qiu-Yun Luo7Yu-Ting Sun8Ming-Yu Lai9Sha-Sha Yuan10Feng-Hua Wang11Hui-Yan Luo12Feng Wang13Yu-Hong Li14Hui-Zhong Zhang15Rui-Hua Xu16Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China; State Key Laboratory of Systems Medicine for Cancer, Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China; Department of Clinical Oncology, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong KongDepartment of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Basic Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. ChinaDepartment of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou 510060, P.R. China; Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, P.R. China; Corresponding authorSummary: Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC.http://www.sciencedirect.com/science/article/pii/S2211124723005879CP: CancerCP: Genomics |
| spellingShingle | Miao-Zhen Qiu Qingjian Chen Dan-Yang Zheng Qi Zhao Qi-Nian Wu Zhi-Wei Zhou Li-Qiong Yang Qiu-Yun Luo Yu-Ting Sun Ming-Yu Lai Sha-Sha Yuan Feng-Hua Wang Hui-Yan Luo Feng Wang Yu-Hong Li Hui-Zhong Zhang Rui-Hua Xu Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins Cell Reports CP: Cancer CP: Genomics |
| title | Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins |
| title_full | Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins |
| title_fullStr | Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins |
| title_full_unstemmed | Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins |
| title_short | Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins |
| title_sort | precise microdissection of gastric mixed adeno neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins |
| topic | CP: Cancer CP: Genomics |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723005879 |
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