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Longitudinal change of genetic variations in cetuximab-treated metastatic colorectal cancer

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Abstract
Recurrent gene mutations and copy number alterations in cancer patients are presumably associated with resistance to targeted therapy. In the present study, we assessed the gene mutations and copy number alterations that recurrently occurred in cetuximab-treated patients with metastatic colorectal cancer (mCRC). Targeted next-generation sequencing was performed in the tumor samples obtained pre-and postcetuximab treatment to assess the variations that occurred during cetuximab treatment. Moreover, we identified the emergent gene mutations (CDK6, EPHA3, ERCC2, MYC, PCMTD1, PIK3CA, PRIM2, RICTOR, and ZNRF3) and copy number alterations (ARAF, BCL2, BRCA2, EGFR, MYC, and SMAD4) that were recurrently observed only in postprogression samples and not in pretreatment or posttreatment samples from patients revealing clinical response. Furthermore, to identify the feasible candidate variations implicated in treatment resistance, we examined the variants with clonal expansion during treatment and discovered PCBP1 as a variant associated with posttreatment progression. Various recurrent mutations were enriched in the TGF-beta signaling pathway. Collectively, we identified recurrent variations in mCRC samples exhibiting post-cetuximab progression. Additionally, future studies are required to evaluate the therapeutic potential of these variations. (c) 2021 Elsevier Inc. All rights reserved.
Author(s)
김권일김선영김정은김태원조수한천성민탁은영홍용상
Issued Date
2021
Type
Article
Keyword
CetuximabColorectal cancerPCBP1TGF-beta
DOI
10.1016/j.cancergen.2021.06.007
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8228
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2555966369&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Longitudinal%20change%20of%20genetic%20variations%20in%20cetuximab-treated%20metastatic%20colorectal%20cancer&offset=0&pcAvailability=true
Publisher
CANCER GENETICS
Location
미국
Language
영어
ISSN
2210-7762
Citation Volume
258
Citation Number
259
Citation Start Page
27
Citation End Page
36
Appears in Collections:
Medicine > Medicine
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