1. Brief report: High prevalence of somatic oncogenic driver alterations in non-small cell lung cancer patients with Li-Fraumeni Syndrome
- Author
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Mezquita, Laura, Jove, Maria, Nadal, Ernest, Kfoury, Maria, Morán, Teresa, Ricordel, Charles, Dhooge, Marion, Tlemsani, Camille, Lena, Hervé, Teulé, Alex, Álvarez, Jose-Valero, Raimbourg, Judith, Hiret, Sandrine, Pharma, Ludovic Lacroix, Menéndez, Mireia, Saldaña, Juana, Brunet, Joan, Lianes, Pilar, Coupier, Isabelle, Auclin, Édouard, Recondo, Gonzalo, Friboulet, Luc, Adam, Julien, Green, Emma, Planchard, David, Frebourg, Thierry, Capellà, Gabriel, Rouleau, Etienne, Lazaro, Conxi, Caron, Olivier, Besse, Benjamin, Institut Gustave Roussy (IGR), Universitat Autònoma de Barcelona (UAB), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), AbbVie, Pfizer, European Society for Medical Oncology, Boehringer Ingelheim, 2017SGR496, Generalitat de Catalunya, Takeda, ADACAP, Merck, Gustave Roussy Cancer Center, Nektar, Sanofi, Onxeo, National Health Institute, Bristol-Myers Squibb, International Association for the Study of Lung Cancer, Roche, Ignyta, Celgene, Merck KGaA, PharmaMar, Taiho Pharmaceutical, AstraZeneca, Novocure, Novartis, Les Laboratories Pierre Fabre, Amgen, PI16/00563, Federación Española de Enfermedades Raras, Spectrum Pharmaceuticals, Ipsen, Biogen, Merck Sharp and Dohme, MedImmune, Eli Lilly and Company, and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Germline TP53 mutation ,ROS1 fusion ,Somatic driver alteration ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Li-Fraumeni syndrome ,EGFR mutation ,NSCLC - Abstract
International audience; Introduction - Actionable somatic molecular alterations are found in 15% to 20% of NSCLC in Europe. NSCLC is a tumor observed in patients with germline TP53 variants causing Li-Fraumeni syndrome (LFS), but its somatic molecular profile is unknown. Methods - Retrospective study of clinical and molecular profiles of patients with NSCLC and germline TP53 variants. Results - Among 22 patients with NSCLC and LFS (n = 23 lung tumors), 64% were women, median age was 51 years, 84% were nonsmokers, 73% had adenocarcinoma histological subtype, and 84% were diagnosed with advanced-stage disease. These patients harbored 16 distinct germline TP53 variants; the most common was p.R158H (5/22; three in the same family). Personal and family histories of cancer were reported in 71% and 90% of patients, respectively. In most cases (87%, 13/15), lung cancer was diagnosed with a late onset. Of the 21 tumors analyzed, somatic oncogenic driver mutations were found in 19 of 21 (90%), EGFR mutations in 18 (exon 19 deletion in 12 cases, L858R in three cases, and G719A, exon 20 insertion, and missing mutation subtype, each with one case), and ROS1 fusion in one case. A PI3KCA mutation was concurrently detected at diagnosis in three EGFR exon 19-deleted tumors (3/12). The median overall survival was 37.3 months in 14 patients treated with EGFR inhibitors; seven developed resistance, five (71%) acquired EGFR-T790M mutation, and one had SCLC transformation. Conclusions - Driver oncogenic alterations were observed in 90% of the LFS tumors, mainly EGFR mutations; one ROS1 fusion was also observed. The germline TP53 variants and lung cancer carcinogenesis driven by oncogenic processes need further evaluation.
- Published
- 2020