Joan Gibert1, Sergi Clavé2, Max Hardy-Werbin1, Álvaro Taus3, Pedro Rocha3, Raquel Longarón2, Gabriel Piquer2, Imane Chaib4, Enric Carcereny4, Teresa Morán4, Marta Salido2, Alba Dalmases2, Beatriz Bellosillo2, Edurne Arriola5. 1. Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain. 2. Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain; Pathology Department, Hospital del Mar, Barcelona, Spain. 3. Medical Oncology Department, Hospital del Mar - CIBERONC, Barcelona, Spain. 4. Medical Oncology Department, Catalan Institute of Oncology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. 5. Cancer Research Program, Hospital del Mar Medical Research Institute, Barcelona, Spain; Medical Oncology Department, Hospital del Mar - CIBERONC, Barcelona, Spain.
Abstract
OBJECTIVES: KRAS mutations are one of the most prevalent alterations in non-small cell lung cancer. However, patients with this driver alteration present heterogeneous clinical outcomes. In this study, we have explored the potential clinical impact of coexisting alterations in this subset of patients. MATERIALS AND METHODS: Samples from a cohort of 69 lung adenocarcinoma patients homogenously treated with platinum doublet as first-line therapy were evaluated using targeted next generation sequencing (NGS). Mutations and copy number alterations were assessed in 37 advanced KRAS-mutant (KRASm) and in 32 KRAS wild-type (KRASwt). RESULTS: TP53 was the most frequent additional alteration found in both cohorts. Interestingly, TP53 mutations were more frequent in KRASwt than in KRASm patients (80 % vs. 34 %; p < 0.05) as well as STK11 mutations (17 % vs 8 %, p=NS). FGFR3 mutations were only found concomitantly with KRASm (11 %). No genomic co-alteration had an impact on overall survival within the KRASm patients treated with chemotherapy. CONCLUSIONS: KRAS mutated lung adenocarcinoma is a heterogeneous entity and comprehensive characterization of co-alterations using NGS may lead to more accurate patient stratification.
OBJECTIVES:KRAS mutations are one of the most prevalent alterations in non-small cell lung cancer. However, patients with this driver alteration present heterogeneous clinical outcomes. In this study, we have explored the potential clinical impact of coexisting alterations in this subset of patients. MATERIALS AND METHODS: Samples from a cohort of 69 lung adenocarcinomapatients homogenously treated with platinum doublet as first-line therapy were evaluated using targeted next generation sequencing (NGS). Mutations and copy number alterations were assessed in 37 advanced KRAS-mutant (KRASm) and in 32 KRAS wild-type (KRASwt). RESULTS:TP53 was the most frequent additional alteration found in both cohorts. Interestingly, TP53 mutations were more frequent in KRASwt than in KRASm patients (80 % vs. 34 %; p < 0.05) as well as STK11 mutations (17 % vs 8 %, p=NS). FGFR3 mutations were only found concomitantly with KRASm (11 %). No genomic co-alteration had an impact on overall survival within the KRASm patients treated with chemotherapy. CONCLUSIONS:KRAS mutated lung adenocarcinoma is a heterogeneous entity and comprehensive characterization of co-alterations using NGS may lead to more accurate patient stratification.
Authors: José Miguel Pardo-Sánchez; Nuria Mancheño; José Cerón; Carlos Jordá; Emilio Ansotegui; Óscar Juan; Sarai Palanca; Antonio Cremades; Carolina Gandía; Rosa Farràs Journal: Cancers (Basel) Date: 2021-06-14 Impact factor: 6.639
Authors: Alberto Pavan; Andrea Boscolo Bragadin; Lorenzo Calvetti; Alessandra Ferro; Elisabetta Zulato; Ilaria Attili; Giorgia Nardo; Alessandro Dal Maso; Stefano Frega; Andrea Giovanni Menin; Matteo Fassan; Fiorella Calabrese; Giulia Pasello; Valentina Guarneri; Giuseppe Aprile; PierFranco Conte; Rafael Rosell; Stefano Indraccolo; Laura Bonanno Journal: Transl Lung Cancer Res Date: 2021-01