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

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.
AuthorsSun Young Kim, Kwoneel Kim, Su Han Cho, Sung-Min Chun, Eunyoung Tak, Yong Sang Hong, Jeong Eun Kim, Tae Won Kim
JournalCancer genetics (Cancer Genet) Vol. 258-259 Pg. 27-36 (11 2021) ISSN: 2210-7762 [Print] United States
PMID34315006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021. Published by Elsevier Inc.
Chemical References
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Cetuximab
Topics
  • Adult
  • Aged
  • Antineoplastic Agents, Immunological (therapeutic use)
  • Biomarkers, Tumor (genetics)
  • Cetuximab (therapeutic use)
  • Colorectal Neoplasms (drug therapy, genetics, pathology)
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local (drug therapy, genetics, pathology)
  • Prognosis
  • Survival Rate

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