'Druggable' alterations detected by Ion Torrent in metastatic colorectal cancer patients

Weijia Fang, Milan Radovich, Yulong Zheng, Cai Yun Fu, Peng Zhao, Chengyu Mao, Yi Zheng, Shusen Zheng

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The frequency and poor prognosis of patients with metastatic colorectal cancer (mCRC) emphasizes the requirement for improved biomarkers for use in the treatment and prognosis of mCRC. In the present study, somatic variants in exonic regions of key cancer genes were identified in mCRC patients. Formalin-fixed, paraffin-embedded tissues obtained by biopsy of the metastases of mCRC patients were collected, and the DNA was extracted and sequenced using the Ion Torrent Personal Genome Machine. For the targeted amplification of known cancer genes, the Ion AmpliSeq™ Cancer Panel, which is designed to detect 739 Catalogue of Somatic Mutations in Cancer (COSMIC) mutations in 604 loci from 46 oncogenes and tumor suppressor genes using as little as 10 ng of input DNA, was used. The sequencing results were then analyzed using the Ampliseq™ Variant Caller plug-in within the Ion Torrent Suite software. In addition, Ingenuity Pathway software was used to perform a pathway analysis. The Cox regression analysis was also conducted to investigate the potential correlation between alteration numbers and clinical factors, including response rate, disease-free survival and overall survival. Among 10 specimens, 65 genetic alterations were identified in 24 genes following the exclusion of germline mutations using the SNP database, whereby 41% of the alterations were also present in the COSMIC database. No clinical factors were found to significantly correlate with the alteration numbers in the patients by statistical analysis. However, pathway analysis identified 'colorectal cancer metastasis signaling' as the most commonly mutated canonical pathway. This analysis further revealed mutated genes in the Wnt, phosphoinositide 3-kinase (PI3K)/AKT and transforming growth factor (TGF)-β/SMAD signaling pathways. Notably, 11 genes, including the expected APC, BRAF, KRAS, PIK3CA and TP53 genes, were mutated in at least two samples. Notably, 90% (9/10) of mCRC patients harbored at least one 'druggable' alteration (range, 1-6 alterations) that has been linked to a clinical treatment option or is currently being investigated in clinical trials of novel targeted therapies. These results indicated that DNA sequencing of key oncogenes and tumor suppressors enables the identification of 'druggable' alterations for individual colorectal cancer patients.

Original languageEnglish (US)
Pages (from-to)1761-1766
Number of pages6
JournalOncology Letters
Volume7
Issue number6
DOIs
StatePublished - Jun 2014

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Keywords

  • Druggable alterations
  • Formalin-fixed paraffin-embedded
  • Ion Torrrent
  • Metastasic colorectal cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fang, W., Radovich, M., Zheng, Y., Fu, C. Y., Zhao, P., Mao, C., Zheng, Y., & Zheng, S. (2014). 'Druggable' alterations detected by Ion Torrent in metastatic colorectal cancer patients. Oncology Letters, 7(6), 1761-1766. https://doi.org/10.3892/ol.2014.2047