Detection of RAS and RAS-associated alterations in primary lung adenocarcinomas. A correlation between molecular findings and tumor characteristics

Irfan Shaukat, Jason J. Kern, Naseruddin Höti, Hui Zhang, Jason Li, Gang Zheng, Frederic B Askin, Edward Gabrielson, Qing Kay Li

Research output: Contribution to journalArticle

Abstract

Rat sarcoma (RAS) and RAS-associated pathways play important roles in the pathogenesis of lung cancers and in the development of targeted therapies. However, the clinical significance of RAS pathways is still not fully understood. We investigated the RAS-associated molecular aberrations in primary lung adenocarcinomas and correlated molecular findings with clinicopathological characteristics of tumors. A total of 220 surgically resected tumors were identified for which a lung cancer molecular panel (testing 7 genes by next-generation sequencing and 3 genes for rearrangement by fluorescence in situ hybridization) had been performed. The overall molecular alterations were detected in 143 cases (65.00%), including 58 cases (26.36%) of KRAS, 40 cases (18.18%) of EGFR, 24 cases (10.91%) of BRAF, 8 cases (3.64%) of PIK3CA, 7 cases (3.18%) of NRAS, 6 cases (2.73%) of ALK alterations. KRAS, BRAF, NRAS, and PIK3CA mutations were more commonly seen in smokers and occurred with much higher rates than previously published data. BRAFV600E mutations were commonly seen in female smokers, whereas, BRAFnon-V600E mutations were seen in both male and female smokers with moderately to poorly differentiated tumors. PIK3CA mutations were predominantly occurred in p.E545K and p.E542K on exon 9 in moderately to poorly differentiated tumors.

Original languageEnglish (US)
Pages (from-to)18-25
Number of pages8
JournalHuman Pathology
Volume84
DOIs
StatePublished - Feb 1 2019

Keywords

  • EGFR
  • KRAS
  • Lung adenocarcinomas (ADC)
  • Non–small cell lung carcinoma (NSCLC)
  • NRAS
  • RAS mutations
  • Targeted therapy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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