Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations
| Autor: | Amit Dutt, Pratik Chandrani, Anuradha Choughule, Kumar Prabhash, Rohit Mishra, Nandini Menon, Rajiv Kumar, Hitesh Kore, Vijay Patil, Supriya Hait, Sanket Desai, Roma Sunder, Amit Joshi, Asim Joshi, Prajish Iyer, Vaishakhi Trivedi, Vanita Noronha |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
druggable mutations medicine.disease_cause whole exome sequencing 03 medical and health sciences 0302 clinical medicine CDKN2A medicine PTEN Exome sequencing mass spectrometry Mutation Lung genetic alterations biology business.industry Cancer medicine.disease stomatognathic diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis lung squamous carcinoma Cancer research biology.protein Adenocarcinoma KRAS business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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