Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach

被引：35

作者：

Liu, Ziyang ^{[1
]}

Wang, Anqiang ^{[2
]}

Pu, Yingying ^{[1
,3
,4
,5
]}

Li, Zhongwu ^{[6
]}

Xue, Ruidong ^{[1
,7
]}

Zhang, Chong ^{[1
]}

Xiang, Xiao ^{[8
]}

Jian-Yu, E. ^{[9
]}

Bu, Zhaode ^{[2
]}

Bai, Fan ^{[1
]}

Ji, Jiafu ^{[2
,10
]}

机构：

[1] Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Sch Life Sci, Beijing, Peoples R China

[2] Peking Univ, Dept Gastrointestinal Surg, Canc Hosp & Inst, Minist Educ,Lab Carcinogenesis & Translat Res, Beijing, Peoples R China

[3] Wuhan Univ, Frontier Sci Ctr Immunol & Metab, Sch Med, Med Res Inst, Wuhan, Peoples R China

[4] Wuhan Univ, Sch & Hosp Stomatol, State Key Lab Breeding Base Basic Sci Stomatol Hu, Wuhan, Peoples R China

[5] Wuhan Univ, Sch & Hosp Stomatol, Minist Educ KLOBM, Key Lab Oral Biomed, Wuhan, Peoples R China

[6] Peking Univ, Dept Pathol, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing, Peoples R China

[7] Peking Univ First Hosp, Translat Canc Res Ctr, Beijing, Peoples R China

[8] Peking Univ Peoples Hosp, Beijing Key Surg Basic Res Lab Liver Cirrhosis &, Dept Hepatobilliary Surg, Beijing, Peoples R China

[9] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[10] Peking Univ, Dept Biobank, Minist Educ, Key Lab Carcinogenesis & Translat Res,Canc Hosp &, Beijing, Peoples R China

来源：

ONCOGENE | 2021年 / 40卷 / 38期

基金：

美国国家科学基金会;

关键词：

STEM-CELLS; TUMOR; CANCER; METASTASIS; METHIONINE; MUTATIONS; CARCINOMA; DIFFERENTIATION; HETEROGENEITY; TRANSITION;

D O I：

10.1038/s41388-021-01976-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hepatoid adenocarcinoma of the stomach (HAS), a rare subtype of gastric cancer (GC), has a low incidence but a high mortality rate. Little is known about the molecular features of HAS. Here we applied whole-exome sequencing (WES) on 58 tumours and the matched normal controls from 54 HAS patients, transcriptome sequencing on 30 HAS tumours, and single-cell RNA sequencing (scRNA-seq) on one HAS tumour. Our results reveal that the adenocarcinomatous component and hepatocellular-like component of the same HAS tumour originate monoclonally, and HAS is likely to initiate from pluripotent precursor cells. HAS has high stemness and high methionine cycle activity compared to classical GC. Two genes in the methionine cycle, MAT2A, and AHCY are potential targets for HAS treatments. We provide the first integrative genomic profiles of HAS, which may facilitate its diagnosis, prognosis, and treatment.

引用

页码：5705 / 5717

页数：13

共 71 条

[11] GOLM1 silencing inhibits the proliferation and motility of human glioblastoma cells via the Wnt/β-catenin signaling pathway [J].

Ding, Xiang ;

Deng, Gang ;

Liu, Junhui ;

Liu, Baohui ;

Yuan, Fan'en ;

Yang, Xue ;

Chen, Qianxue .

BRAIN RESEARCH, 2019, 1717 :117-126

[12] Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data [J].

Favero, F. ;

Joshi, T. ;

Marquard, A. M. ;

Birkbak, N. J. ;

Krzystanek, M. ;

Li, Q. ;

Szallasi, Z. ;

Eklund, A. C. .

ANNALS OF ONCOLOGY, 2015, 26 (01) :64-70

[13] Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5-CD44+ cells [J].

Fu, Dah-Jiun ;

Wang, Lianghai ;

Chouairi, Fouad K. ;

Rose, Ian M. ;

Abetov, Danysh A. ;

Miller, Andrew D. ;

Yamulla, Robert J. ;

Schimenti, John C. ;

Flesken-Nikitin, Andrea ;

Nikitin, Alexander Yu .

NATURE COMMUNICATIONS, 2020, 11 (01)

[14] Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma [J].

Gao, Qiang ;

Zhu, Hongwen ;

Dong, Liangqing ;

Shi, Weiwei ;

Chen, Ran ;

Song, Zhijian ;

Huang, Chen ;

Li, Junqiang ;

Dong, Xiaowei ;

Zhou, Yanting ;

Liu, Qian ;

Ma, Lijie ;

Wang, Xiaoying ;

Zhou, Jian ;

Liu, Yansheng ;

Boja, Emily ;

Robles, Ana I. ;

Ma, Weiping ;

Wang, Pei ;

Li, Yize ;

Ding, Li ;

Wen, Bo ;

Zhang, Bing ;

Rodriguez, Henry ;

Gao, Daming ;

Zhou, Hu ;

Fan, Jia .

CELL, 2019, 179 (02) :561-+

[15] Dietary methionine influences therapy in mouse cancer models and alters human metabolism [J].

Gao, Xia ;

Sanderson, Sydney M. ;

Dai, Ziwei ;

Reid, Michael A. ;

Cooper, Daniel E. ;

Lu, Min ;

Richie, John P., Jr. ;

Ciccarella, Amy ;

Calcagnotto, Ana ;

Mikhael, Peter G. ;

Mentch, Samantha J. ;

Liu, Juan ;

Ables, Gene ;

Kirsch, David G. ;

Hsu, David S. ;

Nichenametla, Sailendra N. ;

Locasale, Jason W. .

NATURE, 2019, 572 (7769) :397-+

[16] Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival [J].

Gaude, Edoardo ;

Frezza, Christian .

NATURE COMMUNICATIONS, 2016, 7

[17] Pan-cancer survey of epithelial-mesenchymal transition markers across the Cancer Genome Atlas [J].

Gibbons, Don L. ;

Creighton, Chad J. .

DEVELOPMENTAL DYNAMICS, 2018, 247 (03) :555-564

[18] GSVA: gene set variation analysis for microarray and RNA-Seq data [J].

Haenzelmann, Sonja ;

Castelo, Robert ;

Guinney, Justin .

BMC BIOINFORMATICS, 2013, 14

[19]

Harvey A, 2019, STEM CELL REP, V13, P573, DOI 10.1016/j.stemcr.2019.09.003

[20]

ISHIKURA H, 1986, CANCER-AM CANCER SOC, V58, P119, DOI 10.1002/1097-0142(19860701)58:1<119::AID-CNCR2820580121>3.0.CO

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