title: Is there a specific phenotype associated with the different subtypes of KRAS mutations in patients with advanced non-small-cell lung cancers?
abstract: OBJECTIVE
  KRAS mutations occur in 20 to 25% of non-small-cell lung cancers (NSCLC) and seem to predict a poor prognosis. There is heterogeneousness in the frequency and spectrum of KRAS mutations, which can be categorized in transitions and transversions. We wondered if subtypes of KRAS mutation were associated with specific clinical phenotypes and specific survival.
  
  
  METHODS
  Between July 2007 and May 2012, patients with advanced NSCLC and KRAS mutation diagnosed in two university hospitals were included. Clinical and histological characteristics, therapeutics and survival data were collected.
  
  
  RESULTS
  Among 635 patients screened for KRAS mutations, 90 were found to be mutated and were included. Median age was 59 years (range: 54-69). Most were males (60%), current or former smokers (63% and 33%, respectively) and had an adenocarcinoma (ADC) (80%). Eighty patients were stage IV and 10 were stage IIIB. Eighty percent of the KRAS mutations were transversions and 20% were transitions. In uni- and multivariate analyses, there was a trend for fewer smokers among patients with transitions than among those with transversions (Odds Ratio [OR]=0.28, 95% CI [0.079-0.999], p=0.05). No significant difference was noted between transitions and transversions for other clinical characteristics. Patients with transitions had more frequently squamous-cell carcinoma (SCC) compared to those with transversions, who had more frequently adenocarcinomas (OR=16.7, 95% CI [2.76-100.8], p=0.002). Seventy-nine patients (86%) had received first-line chemotherapy. No significant difference was seen for disease-control rate, median progression-free survival or overall survival between transitions and transversions.
  
  
  CONCLUSIONS
  A higher proportion of non-smokers and SCC subtypes were observed in the transitions compared to transversions. This confirms the heterogeneity of KRAS mutations and could suggest to expand KRAS testing in SCC to assess impact of RAS in SCC, which remains poorly investigated.
authors.affiliation: Service de Pneumologie, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France.
authors.forename: Coraline
authors.initials: C
authors.lastname: Dumenil
authors.affiliation: Service de Pneumologie, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France; GRC-UPMC 04 Theranoscan, Université Paris 6 Pierre et Marie Curie, 4 place Jussieu, 75252 Paris, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Vieira
authors.affiliation: Service d'Anatomie Pathologique, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Rouleau
authors.affiliation: Service d'Anatomie Pathologique, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.affiliation: GRC-UPMC 04 Theranoscan, Université Paris 6 Pierre et Marie Curie, 4 place Jussieu, 75252 Paris, France; Unité d'Oncologie Thoracique, Service de Pneumologie, Pôle Thorax et Vaisseaux, Hôpital Michallon, CHU de Grenoble, boulevard de la chantourne BP 217, 38043 La Tronche, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Duruisseaux
authors.affiliation: Service de Pneumologie, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France; Service d'Histologie-Biologie Tumorale, Plateforme de génomique des tumeurs solides, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Poulot
authors.affiliation: Service d'Histologie-Biologie Tumorale, Plateforme de génomique des tumeurs solides, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Lacave
authors.affiliation: Service de Pneumologie, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France; GRC-UPMC 04 Theranoscan, Université Paris 6 Pierre et Marie Curie, 4 place Jussieu, 75252 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.affiliation: Département d'oncologie médicale, Institut Curie, 26 rue d'Ulm, Paris, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Massiani
authors.affiliation: Service de Pneumologie, Hôpital Tenon-APHP, Université Paris 6 Pierre et Marie Curie, 4 rue de la Chine, 75970 Paris, France; GRC-UPMC 04 Theranoscan, Université Paris 6 Pierre et Marie Curie, 4 place Jussieu, 75252 Paris, France. Electronic address: marie.wislez@tnn.aphp.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
mesh_terms: D000368:Aged; D000483:Alleles; D015415:Biomarkers; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D003062:Codon; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016017:Odds Ratio; D010641:Phenotype; D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics*
chemical_list: D015415:Biomarkers; D003062:Codon; D018631:ras Proteins
keywords: KRAS mutations; Non-small-cell lung cancer; Squamous-cell carcinoma