Silva, ANS, Coffa, J, Menon, V et al. (19 more authors) (2018) Frequent Coamplification of Receptor Tyrosine Kinase and Downstream Signaling Genes in Japanese Primary Gastric Cancer and Conversion in Matched Lymph Node Metastasis. Annals of Surgery, 267 (1). pp. 114-121. ISSN 0003-4932
Abstract
Objective: To establish the gene copy number status of receptor tyrosine kinase (RTK) and downstream signaling (DSS) genes genes in primary gastric cancer (primGC) and matched lymph node metastases (LNmet). Background: Evidence suggests that coamplification between RTKs and DSSs and conversion between primGC and LNmet are associated with resistance to targeted therapy. Methods: DNA from 237 Japanese primGC and 103 matched LNmet was analyzed using a newly developed multiplex ligation-dependent probe amplification (MLPA) probemix to investigate RTK (EGFR, HER2, FGFR2, and MET) and DSS (PIK3CA, KRAS, MYC, and CCNE1) gene copy number status. Results were compared between primGC and LNmet and related to clinicopathological data including survival. Results: A total of 150 (63%) primGC had either RTK or DSS amplification. DSS coamplification was more frequent than RTK coamplification in primGC and LNmets. Moreover, 70 (30%) GC showed a disconcordant RTK and/or DSS gene copy number status between primGC and LNmet, most common was negative conversion for DSS genes (n=40 GC). The presence of RTK amplification in primGC was related to poorer survival in univariate analysis (P=0.04). Conclusions: This is the first and most comprehensive study in gastric cancer investigating the concordance between gene copy number status of targetable RTKs and downstream signaling oncogenes in primGC and LNmets. Future studies need to establish whether the relative high frequency of RTK and DSS coamplification and/or the relative high rate of negative conversion in LNmet can potentially explain recent failures of RTK targeted therapy in gastric cancer patients.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Wolters Kluwer Health, Inc. This is an author produced version of a paper published in Annals of Surgery. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Pathology & Tumour Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Jan 2017 14:55 |
Last Modified: | 25 Jan 2018 17:20 |
Status: | Published |
Publisher: | Lippincott, Williams & Wilkins |
Identification Number: | 10.1097/SLA.0000000000002042 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:109942 |