Gene Mutation Analysis in EGFR Wild Type NSCLC Responsive to Erlotinib: Are There Features to Guide Patient Selection?

International Journal of Molecular Sciences

Paola Ulivi⁵  Angelo Delmonte⁷  Elisa Chiadini⁵  Daniele Calistri⁵  Maximilian Papi³  Marita Mariotti⁷  Alberto Verlicchi⁸  Angela Ragazzini⁹  Laura Capelli⁵  Alessandro Gamboni⁶  Maurizio Puccetti⁴  Alessandra Dubini¹  Marco Angelo Burgio⁷  Claudia Casanova⁸  Lucio Crinò²  Dino Amadori⁷  Claudio Dazzi⁸ 

[1] Pathology Unit, Morgagni-Pierantoni Hospital, Forlì 47121, Italy; E-Mail:;Division of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia 06156, Italy; E-Mail:;Department of Oncology, Per gli Infermi Hospital, Rimini 47900, Italy; E-Mail:;Pathology Unit, Santa Maria delle Croci Hospital, Ravenna 48121, Italy; E-Mail:;Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy; E-Mails:;Oncology Unit, Degli Infermi Hospital, Faenza 48018, Italy; E-Mail:;Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola 47014, Italy; E-Mails:;Department of Medical Oncology, Santa Maria delle Croci Hospital, Ravenna 48121, Italy; E-Mails:;Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola 47014, Italy; E-Mail:

关键词: NSCLC;    erlotinib;    EGFR wt;    p53;    KRAS;   

DOI  :  10.3390/ijms16010747

来源: mdpi

【 摘 要 】

Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY^® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.