Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations
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Asim Joshi1,4, Rohit Mishra1, Sanket Desai1,4, Pratik Chandrani2,4,5, Hitesh Kore1, Roma Sunder1, Supriya Hait1,4, Prajish Iyer1,4, Vaishakhi Trivedi2,4, Anuradha Choughule2,4, Vanita Noronha2,4, Amit Joshi2,4, Vijay Patil2,4, Nandini Menon2,4, Rajiv Kumar3,4, Kumar Prabhash2,4 and Amit Dutt1,4
1 Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment Research Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra 410210, India
2 Department of Medical Oncology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, Maharashtra 400012, India
3 Department of Pathology, Tata Memorial Centre, Ernest Borges Marg, Parel, Mumbai, Maharashtra 400012, India
4 Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, Maharashtra 410210, India
5 Centre for Computational Biology, Bioinformatics and Crosstalk Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, Maharashtra 410210, India
Keywords: lung squamous carcinoma; genetic alterations; druggable mutations; whole exome sequencing; mass spectrometry
Received: November 24, 2020 Accepted: February 15, 2021 Published: March 16, 2021
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.
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