Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer
Over the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. Certain of these modifications, notably gene alterations known as homologous recombination (HRR) gene...
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| Format: | Article |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1231536/full |
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| author | Fidelis Charles Bugoye Fidelis Charles Bugoye Rispah Torrorey-Sawe Richard Biegon Nazima Dharsee Fidelice M. S. Mafumiko Kirtika Patel Simeon K. Mining |
| author_facet | Fidelis Charles Bugoye Fidelis Charles Bugoye Rispah Torrorey-Sawe Richard Biegon Nazima Dharsee Fidelice M. S. Mafumiko Kirtika Patel Simeon K. Mining |
| author_sort | Fidelis Charles Bugoye |
| collection | DOAJ |
| description | Over the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. Certain of these modifications, notably gene alterations known as homologous recombination (HRR) genes; PALB2, CHEK2 BRCA1, BRCA2, ATM, and genes for DNA mismatch repair (MMR); MLH1, MSH2, MSH6, and PMS2 are connected to a higher risk of prostate cancer and more severe types of the disease. The DNA damage repair (DDR) is essential for constructing and diversifying the antigen receptor genes required for T and B cell development. But this DDR imbalance results in stress on DNA replication and transcription, accumulation of mutations, and even cell death, which compromises tissue homeostasis. Due to these impacts of DDR anomalies, tumor immunity may be impacted, which may encourage the growth of tumors, the release of inflammatory cytokines, and aberrant immune reactions. In a similar vein, people who have altered MMR gene may benefit greatly from immunotherapy. Therefore, for these treatments, mutational genetic testing is indicated. Mismatch repair gene (MMR) defects are also more prevalent than previously thought, especially in patients with metastatic disease, high Gleason scores, and diverse histologies. This review summarizes the current information on the mutation spectrum and clinical significance of DDR mechanisms, such as HRR and MMR abnormalities in prostate cancer, and explains how patient management is evolving as a result of this understanding. |
| first_indexed | 2024-03-12T02:38:09Z |
| format | Article |
| id | doaj.art-3fc4b008d64a48f594e53626cc4cc4e1 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-12T02:38:09Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-3fc4b008d64a48f594e53626cc4cc4e12023-09-04T09:24:29ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-09-011410.3389/fgene.2023.12315361231536Mutational spectrum of DNA damage and mismatch repair genes in prostate cancerFidelis Charles Bugoye0Fidelis Charles Bugoye1Rispah Torrorey-Sawe2Richard Biegon3Nazima Dharsee4Fidelice M. S. Mafumiko5Kirtika Patel6Simeon K. Mining7Government Chemist Laboratory Authority, Directorate of Forensic Science and DNA Services, Dar es Salaam, TanzaniaDepartment of Pathology, Moi Teaching and Referral Hospital, Moi University, Eldoret, KenyaDepartment of Pathology, Moi Teaching and Referral Hospital, Moi University, Eldoret, KenyaDepartment of Pathology, Moi Teaching and Referral Hospital, Moi University, Eldoret, KenyaOcean Road Cancer Institute, Dar es Salaam, TanzaniaGovernment Chemist Laboratory Authority, Directorate of Forensic Science and DNA Services, Dar es Salaam, TanzaniaDepartment of Pathology, Moi Teaching and Referral Hospital, Moi University, Eldoret, KenyaDepartment of Pathology, Moi Teaching and Referral Hospital, Moi University, Eldoret, KenyaOver the past few years, a number of studies have revealed that a significant number of men with prostate cancer had genetic defects in the DNA damage repair gene response and mismatch repair genes. Certain of these modifications, notably gene alterations known as homologous recombination (HRR) genes; PALB2, CHEK2 BRCA1, BRCA2, ATM, and genes for DNA mismatch repair (MMR); MLH1, MSH2, MSH6, and PMS2 are connected to a higher risk of prostate cancer and more severe types of the disease. The DNA damage repair (DDR) is essential for constructing and diversifying the antigen receptor genes required for T and B cell development. But this DDR imbalance results in stress on DNA replication and transcription, accumulation of mutations, and even cell death, which compromises tissue homeostasis. Due to these impacts of DDR anomalies, tumor immunity may be impacted, which may encourage the growth of tumors, the release of inflammatory cytokines, and aberrant immune reactions. In a similar vein, people who have altered MMR gene may benefit greatly from immunotherapy. Therefore, for these treatments, mutational genetic testing is indicated. Mismatch repair gene (MMR) defects are also more prevalent than previously thought, especially in patients with metastatic disease, high Gleason scores, and diverse histologies. This review summarizes the current information on the mutation spectrum and clinical significance of DDR mechanisms, such as HRR and MMR abnormalities in prostate cancer, and explains how patient management is evolving as a result of this understanding.https://www.frontiersin.org/articles/10.3389/fgene.2023.1231536/fullmutationDNA damageprostate cancermismatchrepair-deficientlandscape |
| spellingShingle | Fidelis Charles Bugoye Fidelis Charles Bugoye Rispah Torrorey-Sawe Richard Biegon Nazima Dharsee Fidelice M. S. Mafumiko Kirtika Patel Simeon K. Mining Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer Frontiers in Genetics mutation DNA damage prostate cancer mismatch repair-deficient landscape |
| title | Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer |
| title_full | Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer |
| title_fullStr | Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer |
| title_full_unstemmed | Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer |
| title_short | Mutational spectrum of DNA damage and mismatch repair genes in prostate cancer |
| title_sort | mutational spectrum of dna damage and mismatch repair genes in prostate cancer |
| topic | mutation DNA damage prostate cancer mismatch repair-deficient landscape |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1231536/full |
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