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Updated: May 7, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
CDKN2A exon-wise deletion status and novel somatic mutations in Indian glioma patients
M K Sibin1, Dhananjaya I Bhat, Ch Lavanya
1Department of Human Genetics, National Institute of Mental Health and Neuro Sciences, Bangalore, 560029, India.
Abstract:
Over the years, deletions of CDKN2A (p16) tumor suppressor gene has been studied using FISH and multiplex PCR, with major focus on exon 2 in various cancers, and the frequency of mutation is found to be varied in different studies. In this study, we analyzed the deletion status of all three exons of p16 and frequency of exon 2 somatic point mutations in glioma from the Indian population and its clinical implications. Multiplex PCR was carried out in order to check deletion of all 3 exons in 50 glioma samples. Nonconventional PCR-SSCP analysis and sequencing was done to identify mutations in 48 cases. Deletion of at least one of the three exons of p16 INK4A was observed in ten cases (20 %). The frequencies of exon-wise deletions were 10 % for exon 1, 4 % for exon 2, and 8 % for exon 3. Two out of 48 samples were positive for mutations in p16 exon 2. One sample had a transition of G to C on position 147 with a codon change TGG to TGC which does not contribute to the protein structure. Another sample had a transversion of A to G on the position 154 with a codon change ATG to GTG with change in amino acid methionine to valine in 52nd position. Deletion pattern was found to be varied in three exons. Frequency of p16 gene mutation was less in the Indian population (4.2 %), and this mutation does not contribute to any remarkable change in protein structure.
Insights
This study investigated the CDKN2A (p16) tumor suppressor gene in Indian glioma patients. Deletions were found in 20% of cases, with low mutation frequency and minimal protein impact.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The CDKN2A (p16) tumor suppressor gene is crucial in various cancers.
- Previous studies focused on p16 exon 2 deletions, yielding varied mutation frequencies.
- Understanding p16 alterations in glioma is vital for targeted therapies.
Purpose of the Study:
- To analyze p16 gene deletion status across all three exons in Indian glioma patients.
- To determine the frequency of p16 exon 2 somatic point mutations.
- To investigate the clinical implications of p16 alterations in glioma.
Main Methods:
- Multiplex PCR was used to detect deletions in all three p16 exons in 50 glioma samples.
- PCR-Single Strand Conformation Polymorphism (PCR-SSCP) and sequencing identified mutations in 48 samples.
- Analysis focused on exon-wise deletion patterns and specific point mutations.
Main Results:
- p16 INK4A deletion was observed in 20% of glioma cases (10% exon 1, 4% exon 2, 8% exon 3).
- A low frequency of p16 exon 2 mutations (4.2%) was detected in the Indian population.
- Identified mutations had minimal impact on protein structure, with one altering an amino acid without significant consequence.
Conclusions:
- p16 deletion patterns vary across its three exons in Indian glioma.
- The low mutation rate of p16 in this population suggests a potentially different role compared to other ethnicities.
- Further research is needed to fully elucidate the clinical significance of p16 alterations in glioma.
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