G48A, a new KRAS mutation found in lung adenocarcinoma

Mirko Marabese, Elisa Caiola, Marina C. Garassino, Giulio Rastelli, Giulio Settanni, Sonia Brugnara, Massimo Broggini, Monica Ganzinelli

Research output: Contribution to journalArticle

Abstract

A new somatic mutation in the coding region of Kirsten rat sarcoma viral oncogene homolog gene (KRAS), G48A, has been identified in a patient with non-small cell lung cancer (NSCLC). No other mutations were found by screening several genes known to be mutated in NSCLC. The patient responded to first-line therapy and is still under maintenance treatment 18 months after diagnosis. Normal and cancer cells were engineered to express the KRAS(G48A) mutation. KRAS(G48A) overexpression did not change the growth or the response to treatment compared with KRAS(wild type)-expressing cells. Analysis of the structure of the KRAS(G48A) mutant predicted altered interactions with other proteins. Analysis of KRAS binding to B-Raf proto-oncogene, serine/threonine kinase showed that the KRAS(G48A) mutant behaves more like a wild-type than a classical KRAS(G12) mutant. In conclusion, this new mutation in the coding region of KRAS, found in NSCLC, does not induce phenotypic changes similar to those induced by G12 mutants but presumably affects KRAS binding to proteins other than B-Raf proto-oncogene, serine/threonine kinase.

Original languageEnglish
Pages (from-to)1170-1175
Number of pages6
JournalJournal of Thoracic Oncology
Volume11
Issue number7
DOIs
Publication statusPublished - 2016

Keywords

  • Adenocarcinoma
  • Gene mutation
  • KRAS
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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