Prognostic significance of frequent CLDN18-ARHGAP26/6 fusion in gastric signet-ring cell cancer

Autor: Lunzhi Dai, Yong Peng, Yang Shu, Shouyue Zhang, Gu He, Meng Qiu, Xuyang Xia, Dan Jiang, Ping Wang, Heng Xu, Xueyan Zhou, Peiqi Wang, Xiao-Long Chen, Xiao-Hai Song, Dan Xie, Bin Zheng, Yongsheng Wang, Kun Yang, Biao Dong, Yinglan Zhao, Senlin Yin, Qianqian Hou, Weimin Li, Wei-Han Zhang, Bo Liu, Dandan Yin, Jian-Kang Zhou, Hongye Sun, Fei Liao, Wei Zhang, Hua Cheng, Xin-Zu Chen, Leilei Fu, Junlong Zhang, Yunfei An, Xianghui Fu, Zong-Guang Zhou, Jiankun Hu, Jian-Ping Liu, Lan Zhang, Duyu Zhang, Yan Zhang, Hanshuo Yang, Wei Cheng, Y. Wang, Yuquan Wei, Li Yang, Liang Ouyang, Lin-Yong Zhao
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
Male
medicine.medical_specialty
Science
medicine.medical_treatment
Mutant Chimeric Proteins
General Physics and Astronomy
Antineoplastic Agents
medicine.disease_cause
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
0302 clinical medicine
Stomach Neoplasms
Internal medicine
Cell Line
Tumor
Carcinoma
medicine
Humans
Stage (cooking)
lcsh:Science
Retrospective Studies
Chemotherapy
Multidisciplinary
Whole Genome Sequencing
Signet ring cell
business.industry
GTPase-Activating Proteins
Cancer
Retrospective cohort study
General Chemistry
medicine.disease
digestive system diseases
Oxaliplatin
030104 developmental biology
Treatment Outcome
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Claudins
lcsh:Q
Female
Carcinogenesis
business
Carcinoma
Signet Ring Cell
medicine.drug
Zdroj: Nature Communications
Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018)
ISSN: 2041-1723
Popis: Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.
Signet-ring cell carcinoma (SRCC) is a unique type of gastric cancer with no prognostic features. Here, the authors report a CLDN18-ARHGAP26/6 gene fusion in patients with a high signet-ring cell content, poor survival outcomes, and who experience no benefit from platinum/fluoropyrimidines-based chemotherapy.
Databáze: OpenAIRE
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