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Research Papers:

Impact of country of birth on genetic testing of metastatic lung adenocarcinomas in France: African women exhibit a mutational spectrum more similar to Asians than to Caucasians

Raphael Saffroy, Jean-François Morère, Nelly Bosselut, Pasquale F. Innominato, Jocelyne Hamelin, Jean Trédaniel, Sophie Masse, Véronique Dussaule-Duchatelle, André Balaton, Pierre Validire, Catherine Guettier, Mohamed Bouchahda and Antoinette Lemoine _

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Oncotarget. 2017; 8:50792-50803. https://doi.org/10.18632/oncotarget.15132

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Abstract

Raphael Saffroy1,2, Jean-François Morère2,3, Nelly Bosselut1,2, Pasquale F. Innominato3,4,5,6, Jocelyne Hamelin1,2, Jean Trédaniel7, Sophie Masse8, Véronique Dussaule-Duchatelle9, André Balaton9,10, Pierre Validire11, Catherine Guettier12, Mohamed Bouchahda3,13 and Antoinette Lemoine1,2

1AP-HP, GH Paris-Sud, Hôpital Paul Brousse, Department of Biochiemistry and Oncogenetics, Platform Oncomolpath/INCa, Villejuif, France

2INSERM UMR-S 1193, Université Paris-Sud, Université Paris-Saclay, Villejuif, France

3AP-HP, GH Paris-Sud, Hôpital Paul Brousse, Department of Medical Oncology, Villejuif, France

4INSERM UMR-935, Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France

5Cancer Chronotherapy Unit, Cancer Research Centre, Warwick Medical School, University of Warwick, Coventry, United Kingdom

6Department of Oncology, Queen Elizabeth Hospital Birmingham NHS Foundation Trust, Birmingham, United Kingdom

7Hôpital Saint Joseph, Department of Respiratory Medicine, Université Paris 5, Paris, France

8Groupe Hospitalier Nord Essonne, Department of Pathology, Longjumeau, France

9Hôpital Saint Joseph, Department of Pathology, Paris, France

10ACP Bievres-les Ulis, Department of Pathology, Les Ulis, France

11Institut Mutualiste Montsouris, Department of Pathology, Paris, France

12AP-HP, GH Paris-Sud, Hôpital Paul Brousse, Department of Pathology, Platform Oncomolpath/INCa, Villejuif, France

13Ramsay-GDS Clinique du Mousseau, Department of Medical Oncology, Evry, France

Correspondence to:

Antoinette Lemoine, email: antoinette.lemoine@aphp.fr

Keywords: NSCLC, genetic testing, genotype, EGFR, ERBB2

Received: November 01, 2016     Accepted: January 09, 2017     Published: February 07, 2017

ABSTRACT

Background: Limited data are available on the prevalence of oncogenic driver mutations in Caucasian populations, and especially in Europeans.

Aim: To evaluate the targetable mutational spectra in unselected patients with lung adenocarcinoma in routine clinical practice from several French hospitals, using the same molecular platform.

Patients and Methods: Samples from 2,219 consecutive patients with histologically-proven advanced lung adenocarcinoma were centrally analysed at a referenced and certified diagnostic platform in order to test for activating and resistance mutations in EGFR, KRAS, BRAF, ERBB2 and PI3KCA. Demographic and clinical features were retrieved from the medical charts. Multivariate binary logistic regression was used to determine the independent predictive factors for the occurrence of specific mutations, in the whole study population or in selected subgroups.

Findings: The overall respective incidence of EGFR, KRAS, BRAF, ERBB2 and PI3KCA mutations was 10.5%, 0.9%, 25%, 1.5%, 2.1% and 1.4%, in our study sample including 87.4% white Caucasians, 10.8% Africans and 1.8% Asians; 60.6% men, 30.7% never smoker (median age: 68.3 years). Ethnicity was an independent predictor for EGFR, KRAS and ERBB2 gene abnormalities. In all cases, a significantly higher prevalence of targetable EGFR and ERBB2, and a lower prevalence of resistance KRAS mutations were observed in African women as compared to African men or Caucasians.

Conclusions: In real life conditions of routine genetic testing, we have identified subsets of patients with specific targetable activating somatic mutations according to ethnicity, who could preferentially benefit from anti-EGFR and anti-ERBB2 targeted therapies.


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PII: 15132