Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer
It is now known that at least 10% of samples with pancreatic cancers (PC) contain a causative mutation in the known susceptibility genes, suggesting the importance of identifying cancer-associated genes that carry the causative mutations in high-risk individuals for early detection of PC. In this st...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4376 |
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| author | Amin Ghareyazi Amir Mohseni Hamed Dashti Amin Beheshti Abdollah Dehzangi Hamid R. Rabiee Hamid Alinejad-Rokny |
| author_facet | Amin Ghareyazi Amir Mohseni Hamed Dashti Amin Beheshti Abdollah Dehzangi Hamid R. Rabiee Hamid Alinejad-Rokny |
| author_sort | Amin Ghareyazi |
| collection | DOAJ |
| description | It is now known that at least 10% of samples with pancreatic cancers (PC) contain a causative mutation in the known susceptibility genes, suggesting the importance of identifying cancer-associated genes that carry the causative mutations in high-risk individuals for early detection of PC. In this study, we develop a statistical pipeline using a new concept, called gene-motif, that utilizes both mutated genes and mutational processes to identify 4211 3-nucleotide PC-associated gene-motifs within 203 significantly mutated genes in PC. Using these gene-motifs as distinguishable features for pancreatic cancer subtyping results in identifying five PC subtypes with distinguishable phenotypes and genotypes. Our comprehensive biological characterization reveals that these PC subtypes are associated with different molecular mechanisms including unique cancer related signaling pathways, in which for most of the subtypes targeted treatment options are currently available. Some of the pathways we identified in all five PC subtypes, including cell cycle and the Axon guidance pathway are frequently seen and mutated in cancer. We also identified Protein kinase C, EGFR (epidermal growth factor receptor) signaling pathway and P53 signaling pathways as potential targets for treatment of the PC subtypes. Altogether, our results uncover the importance of considering both the mutation type and mutated genes in the identification of cancer subtypes and biomarkers. |
| first_indexed | 2024-03-10T08:14:32Z |
| format | Article |
| id | doaj.art-59f7e013491e4a87beaa8f39594ad915 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:14:32Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-59f7e013491e4a87beaa8f39594ad9152023-11-22T10:26:29ZengMDPI AGCancers2072-66942021-08-011317437610.3390/cancers13174376Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic CancerAmin Ghareyazi0Amir Mohseni1Hamed Dashti2Amin Beheshti3Abdollah Dehzangi4Hamid R. Rabiee5Hamid Alinejad-Rokny6Bioinformatics and Computational Biology Laboratory, Sharif University of Technology, Tehran 11365, IranBioinformatics and Computational Biology Laboratory, Sharif University of Technology, Tehran 11365, IranBioinformatics and Computational Biology Laboratory, Sharif University of Technology, Tehran 11365, IranDepartment of Computing, Macquarie University, Sydney, NSW 2109, AustraliaDepartment of Computer Science, Rutgers University, Camden, NJ 08102, USABioinformatics and Computational Biology Laboratory, Sharif University of Technology, Tehran 11365, IranBioMedical Machine Learning Lab (BML), The Graduate School of Biomedical Engineering, The University of New South Wales, Sydney, NSW 2052, AustraliaIt is now known that at least 10% of samples with pancreatic cancers (PC) contain a causative mutation in the known susceptibility genes, suggesting the importance of identifying cancer-associated genes that carry the causative mutations in high-risk individuals for early detection of PC. In this study, we develop a statistical pipeline using a new concept, called gene-motif, that utilizes both mutated genes and mutational processes to identify 4211 3-nucleotide PC-associated gene-motifs within 203 significantly mutated genes in PC. Using these gene-motifs as distinguishable features for pancreatic cancer subtyping results in identifying five PC subtypes with distinguishable phenotypes and genotypes. Our comprehensive biological characterization reveals that these PC subtypes are associated with different molecular mechanisms including unique cancer related signaling pathways, in which for most of the subtypes targeted treatment options are currently available. Some of the pathways we identified in all five PC subtypes, including cell cycle and the Axon guidance pathway are frequently seen and mutated in cancer. We also identified Protein kinase C, EGFR (epidermal growth factor receptor) signaling pathway and P53 signaling pathways as potential targets for treatment of the PC subtypes. Altogether, our results uncover the importance of considering both the mutation type and mutated genes in the identification of cancer subtypes and biomarkers.https://www.mdpi.com/2072-6694/13/17/4376pancreatic cancercancer subtype identificationsomatic point mutationsgenotype and phenotype characterizationtherapeutic targetspersonalized medicine |
| spellingShingle | Amin Ghareyazi Amir Mohseni Hamed Dashti Amin Beheshti Abdollah Dehzangi Hamid R. Rabiee Hamid Alinejad-Rokny Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer Cancers pancreatic cancer cancer subtype identification somatic point mutations genotype and phenotype characterization therapeutic targets personalized medicine |
| title | Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer |
| title_full | Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer |
| title_fullStr | Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer |
| title_full_unstemmed | Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer |
| title_short | Whole-Genome Analysis of De Novo Somatic Point Mutations Reveals Novel Mutational Biomarkers in Pancreatic Cancer |
| title_sort | whole genome analysis of de novo somatic point mutations reveals novel mutational biomarkers in pancreatic cancer |
| topic | pancreatic cancer cancer subtype identification somatic point mutations genotype and phenotype characterization therapeutic targets personalized medicine |
| url | https://www.mdpi.com/2072-6694/13/17/4376 |
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