Asim Joshi1,2, Rohit Mishra1, Sanket Desai1,2, Pratik Chandrani3,2,4, Hitesh Kore1, Roma Sunder1, Supriya Hait1,2, Prajish Iyer1,2, Vaishakhi Trivedi3,2, Anuradha Choughule3,2, Vanita Noronha3,2, Amit Joshi3,2, Vijay Patil3,2, Nandini Menon3,2, Rajiv Kumar5,2, Kumar Prabhash3,2, Amit Dutt1,2. 1. Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment Research Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra 410210, India. 2. Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, Maharashtra 410210, India. 3. Department of Medical Oncology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, Maharashtra 400012, India. 4. Centre for Computational Biology, Bioinformatics and Crosstalk Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, Maharashtra 410210, India. 5. Department of Pathology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, Maharashtra 400012, India.
Abstract
INTRODUCTION: Unlike lung adenocarcinoma patients, there is no FDA-approved targeted-therapy likely to benefit lung squamous cell carcinoma patients. MATERIALS AND METHODS: We performed survival analyses of lung squamous cell carcinoma patients harboring therapeutically relevant alterations identified by whole exome sequencing and mass spectrometry-based validation across 430 lung squamous tumors. RESULTS: We report a mean of 11.6 mutations/Mb with a characteristic smoking signature along with mutations in TP53 (65%), CDKN2A (20%), NFE2L2 (20%), FAT1 (15%), KMT2C (15%), LRP1B (15%), FGFR1 (14%), PTEN (10%) and PREX2 (5%) among lung squamous cell carcinoma patients of Indian descent. In addition, therapeutically relevant EGFR mutations occur in 5.8% patients, significantly higher than as reported among Caucasians. In overall, our data suggests 13.5% lung squamous patients harboring druggable mutations have lower median overall survival, and 19% patients with a mutation in at least one gene, known to be associated with cancer, result in significantly shorter median overall survival compared to those without mutations. CONCLUSIONS: We present the first comprehensive landscape of genetic alterations underlying Indian lung squamous cell carcinoma patients and identify EGFR, PIK3CA, KRAS and FGFR1 as potentially important therapeutic and prognostic target. Copyright:
INTRODUCTION: Unlike lung adenocarcinomapatients, there is no FDA-approved targeted-therapy likely to benefit lung squamous cell carcinomapatients. MATERIALS AND METHODS: We performed survival analyses of lung squamous cell carcinomapatients harboring therapeutically relevant alterations identified by whole exome sequencing and mass spectrometry-based validation across 430 lung squamous tumors. RESULTS: We report a mean of 11.6 mutations/Mb with a characteristic smoking signature along with mutations in TP53 (65%), CDKN2A (20%), NFE2L2 (20%), FAT1 (15%), KMT2C (15%), LRP1B (15%), FGFR1 (14%), PTEN (10%) and PREX2 (5%) among lung squamous cell carcinomapatients of Indian descent. In addition, therapeutically relevant EGFR mutations occur in 5.8% patients, significantly higher than as reported among Caucasians. In overall, our data suggests 13.5% lung squamouspatients harboring druggable mutations have lower median overall survival, and 19% patients with a mutation in at least one gene, known to be associated with cancer, result in significantly shorter median overall survival compared to those without mutations. CONCLUSIONS: We present the first comprehensive landscape of genetic alterations underlying Indian lung squamous cell carcinomapatients and identify EGFR, PIK3CA, KRAS and FGFR1 as potentially important therapeutic and prognostic target. Copyright: