ArticleMolecular medicine (Cambridge, Mass.)2020
A novel hotspot and rare somatic mutation p.A138V, at TP53 is associated with poor survival of pancreatic ductal and periampullary adenocarcinoma patients.
Article in Molecular medicine (Cambridge, Mass.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 24 citations in OpenAlex.
- Targeted Therapy in Pancreatic Ductal Adenocarcinoma: Current Advances and Challenges.Current oncology (Toronto, Ont.) · 2026Review
- Identification of a chromatin-modifying gene-histone lysine N-methyl transferase (KMT2C/MLL3) as a potential immunomodulator oncogene in Indian pancreatic cancer patients.European journal of medical research · 2025Article
- Identification of KCNJ5 gene an adverse prognosis associated novel onco-ionchannel in Indian pancreatic cancer cohort.Discover oncology · 2025Article
- Review
- Mutant Pattern of p53 as a Feasible Predictor of Distant Metastasis Following Curative Gastrectomy for Advanced-stage Gastric Cancer.Journal of Cancer · 2025Article
- Oncometabolites in pancreatic cancer: Strategies and its implications.World journal of experimental medicine · 2024Review
- Combining evolution and protein language models for an interpretable cancer driver mutation prediction with D2Deep.Briefings in bioinformatics · 2024Article
- Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review.Cancers · 2023Review
- Loss of fragile WWOX gene leads to senescence escape and genome instability.Cellular and molecular life sciences : CMLS · 2023Article
- Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways.World journal of gastrointestinal oncology · 2023Review
- Emerging role of non-invasive and liquid biopsy biomarkers in pancreatic cancer.World journal of gastroenterology · 2023Review
- DNA methylome in pancreatic cancer identified novel promoter hyper-methylation in NPY and FAIM2 genes associated with poor prognosis in Indian patient cohort.Cancer cell international · 2022Article
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Authors and funding
18 authors at 5 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5-2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now.
methodsTargeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured.
resultsAmong the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients.
conclusionDetection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.
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