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Updated: Nov 10, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations
Asim Joshi1,2, Rohit Mishra1, Sanket Desai1,2
1Integrated Cancer Genomics Laboratory, Advanced Centre for Treatment Research Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra 410210, India.
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.
Insights
This study analyzes genetic mutations in Indian lung squamous cell carcinoma patients, finding specific mutations like EGFR are more common and impact survival. These findings highlight potential new therapeutic targets for lung cancer.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Lung squamous cell carcinoma (LSCC) lacks FDA-approved targeted therapies, unlike lung adenocarcinoma.
- Identifying actionable mutations is crucial for developing new LSCC treatments.
Purpose of the Study:
- To comprehensively analyze the genetic landscape of LSCC in Indian patients.
- To identify therapeutically relevant genetic alterations and their prognostic significance.
Main Methods:
- Whole exome sequencing and mass spectrometry were used to analyze 430 LSCC tumors.
- Survival analyses were performed on patients with identified genetic alterations.
Main Results:
- A high mutation rate (11.6 mutations/Mb) with a smoking signature was observed.
- Frequent mutations include TP53 (65%), CDKN2A (20%), NFE2L2 (20%), and FGFR1 (14%).
- Therapeutically relevant EGFR mutations (5.8%) were more prevalent than in Caucasian populations, and patients with druggable mutations showed reduced overall survival.
Conclusions:
- This is the first comprehensive genetic landscape of Indian LSCC patients.
- EGFR, PIK3CA, KRAS, and FGFR1 are identified as potential therapeutic and prognostic targets.
