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

Journal: Nature Communications

Published: 2018-06-30

DOI: 10.1038/s41467-018-04907-0

Affiliations: 19

Authors: 49

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Research Highlight

A genetic bellwether for stomach cancer

© Science Photo Library – SCIEPRO/Brand X Pictures/Getty

© Science Photo Library – SCIEPRO/Brand X Pictures/Getty

A rare type of stomach cancer frequently features a genomic aberration that renders tumours more aggressive and less likely to respond to drug treatment.

A Sichuan University–led team performed whole-genome sequencing on tumour samples and healthy tissue from 32 patients with signet-ring cell cancer (SRCC), a form of gastric cancer that mostly affects glandular cells of the stomach lining. They found that 25 per cent of the tumour DNA contained a fusion between the same two genes, CLDN18 and ARHGAP26. This structural change to the genome is thought to contribute to the invasiveness of gastric cancer cells.

The researchers sequenced another 797 tumours from Chinese patients with gastric cancer and identified this same genetic fusion in 65 samples, 57 of which came from patients with the SRCC form of the disease. Patients who carried the gene fusion also had worse outcomes, on average, and were less likely to benefit from standard chemotherapy. 

The findings highlight the potential value of testing for this genomic rearrangement to guide clinical decision-making for gastric cancer, the second most common cause of cancer death in Asia.

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  1. Nature Communications 9, 2447 (2018). doi: 10.1038/s41467-018-04907-0
Institutions Share
Cancer Center, WCSM/WCH SCH, China 0.53
Precision Medicine Center, WCSM/WCH SCH, China 0.10
WuXi NextCODE Shanghai, China 0.06
Department of Gastrointestinal Surgery, WCSM/WCH SCH, China 0.06
Institute of Gastric Cancer, WCSM/WCH SCH, China 0.06
West China School of Medicine/West China Hospital of Sichuan University (WCSM/WCH), SCU, China 0.05
Department of Pathology, WCSM/WCH SCU, China 0.04
State Key Laboratory of Oral Diseases, SCU, China 0.02
Saul R. Korey Department of Neurology, Einstein, United States of America (USA) 0.02
Department of Respiratory Medicine, WCSM/WCH SCU, China 0.02
Department of Thoracic Oncology, WCSM/WCH SCH, China 0.01
Department of Clinical Pharmacology, CSU, China 0.01
Hunan Provincial Key Laboratory of Pharmacogenetics at Xiangya Hospital, CSU, China 0.01
Department of Abdominal Cancer, WCSM/WCH SCU, China 0.01