The clinical significance of ras, pik3ca, and pten mutations in non-small cell lung cancer using cell-free dna

Won Jin Chang, Jae Sook Sung, Sung Yong Lee, Eun Joo Kang, Nak Jung Kwon, Hae Mi Kim, Sang Won Shin, Jung Yoon Choi, Yoon Ji Choi, Ju Won Kim, Kyong Hwa Park, Yeul Hong Kim

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Mutations in the EGFR gene downstream signaling pathways may cause receptor-independent pathway activation, making tumors unresponsive to EGFR inhibitors. However, the clinical significance of RAS, PIK3CA or PTEN mutations in NSCLC is unclear. In this study, patients who were initially diagnosed with NSCLC or experienced recurrence after surgical resection were enrolled, and blood samples was collected. Ultra-deep sequencing analysis of cfDNA using Ion AmpliSeq Cancer Hotspot Panel v2 with Proton platforms was conducted. RAS/PIK3CA/PTEN mutations were frequently detected in cfDNA in stage IV NSCLC (58.1%), and a high proportion of the patients (47.8%) with mutations had bone metastases at diagnosis. The frequency of RAS/PIK3CA/PTEN mutations in patients with activating EGFR mutation was 61.7%. The median PFS for EGFR-TKIs was 15.1 months in patients without RAS/PIK3CA/PTEN mutations, and 19.9 months in patients with mutations (p = 0.549). For patients with activating EGFR mutations, the overall survival was longer in patients without RAS/PIK3CA/PTEN mutations (53.8 months vs. 27.4 months). For the multivariate analysis, RAS/PIK3CA/PTEN mutations were independent predictors of poor prognosis in patients with activating EGFR mutations. In conclusion, RAS, PIK3CA and PTEN mutations do not hamper EGFR-TKI treatment outcome; however, they predict a poor OS when activating EGFR mutations coexist.

Original languageEnglish
Article number2642
Pages (from-to)1-14
Number of pages14
JournalJournal of Clinical Medicine
Volume9
Issue number8
DOIs
Publication statusPublished - 2020 Aug

Bibliographical note

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Cell-free DNA
  • Lung cancer
  • Mutations
  • Sequencing

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'The clinical significance of ras, pik3ca, and pten mutations in non-small cell lung cancer using cell-free dna'. Together they form a unique fingerprint.

Cite this