V Fallet1, R Saffroy2, N Girard3, J Mazieres4, S Lantuejoul5, T Vieira1, I Rouquette6, F Thivolet-Bejui7, M Ung4, V Poulot1, L Schlick1, D Moro-Sibilot8, M Antoine9, J Cadranel10, A Lemoine2, M Wislez11. 1. GRC n°04, Theranoscan, Sorbonne Universités, UPMC Université de Paris 06, Paris. 2. INSERM U1004, Université de Paris 11, Institut André Wolf, Villejuif Department of Biochemistry and Molecular Biology, AP-HP, Hôpital Paul Brousse, Villejuif. 3. Pulmonary Medicine Unit, Hôpital Louis Pradel, Hospices Civils, Lyon. 4. Pulmonary Medicine Unit, Hôpital Larrey, Centre Hospitalier Universitaire, Université de Toulouse III, Toulouse. 5. Department of Pathology, Hôpital A. Michallon, Centre Hospitalier Universitaire, Grenoble. 6. Department of Pathology, Centre Hospitalier Universitaire Rangueil, Toulouse. 7. Department of Pathology, Hôpital Louis Pradel, Lyon. 8. Pulmonary Medicine Unit, Hôpital A. Michallon, Centre Hospitalier Universitaire, Grenoble. 9. GRC n°04, Theranoscan, Sorbonne Universités, UPMC Université de Paris 06, Paris Department of Pathology, AP-HP, Hôpital Tenon, Paris. 10. GRC n°04, Theranoscan, Sorbonne Universités, UPMC Université de Paris 06, Paris Pulmonary Medicine Unit, AP-HP, Hôpital Tenon, Paris, France. 11. GRC n°04, Theranoscan, Sorbonne Universités, UPMC Université de Paris 06, Paris Pulmonary Medicine Unit, AP-HP, Hôpital Tenon, Paris, France marie.wislez@tnn.aphp.fr.
Abstract
BACKGROUND: Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology. PATIENTS AND METHODS: We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes. RESULTS: In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold. CONCLUSION: Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.
BACKGROUND:Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology. PATIENTS AND METHODS: We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes. RESULTS: In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold. CONCLUSION: Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.