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Genomic Instability

MedGen UID:
182518
•Concept ID:
C0919532
•
Cell or Molecular Dysfunction
Synonyms: Genome Instabilities; Genome Instability; Genomic Instabilities; Instabilities, Genome; Instabilities, Genomic; Instability, Genome; Instability, Genomic

Definition

A biological process consisting of chromosomal rearrangements and duplications. These phenotypes are often seen in the karyotype of cancer cells, where there is an imbalance between the mechanisms of cell-cycle control and mutation rates within aberrant genes. Ataxia telangiectasia is a disease that is resultant from mutations in the ATM gene, which is a cell cycle checkpoint gene. Nijmegen breakage syndrome is also a disease characterized by chromosomal and genomic instability. [from NCI]

Professional guidelines

PubMed

Molecular Genetics of Prostate Cancer and Role of Genomic Testing.
Akhoundova D, Feng FY, Pritchard CC, Rubin MA
Surg Pathol Clin 2022 Dec;15(4):617-628. Epub 2022 Oct 13 doi: 10.1016/j.path.2022.08.002. PMID: 36344179
PARP and PARG inhibitors in cancer treatment.
Slade D
Genes Dev 2020 Mar 1;34(5-6):360-394. Epub 2020 Feb 6 doi: 10.1101/gad.334516.119. PMID: 32029455Free PMC Article
Genotype-phenotype associations in Fanconi anemia: A literature review.
Fiesco-Roa MO, Giri N, McReynolds LJ, Best AF, Alter BP
Blood Rev 2019 Sep;37:100589. Epub 2019 Jul 16 doi: 10.1016/j.blre.2019.100589. PMID: 31351673Free PMC Article

Recent clinical studies

Etiology

Helicobacter pylori and Gastric Cancer: Pathogenetic Mechanisms.
Salvatori S, Marafini I, Laudisi F, Monteleone G, Stolfi C
Int J Mol Sci 2023 Feb 2;24(3) doi: 10.3390/ijms24032895. PMID: 36769214Free PMC Article
Mediterranean diet and the hallmarks of ageing.
Shannon OM, Ashor AW, Scialo F, Saretzki G, Martin-Ruiz C, Lara J, Matu J, Griffiths A, Robinson N, Lillà L, Stevenson E, Stephan BCM, Minihane AM, Siervo M, Mathers JC
Eur J Clin Nutr 2021 Aug;75(8):1176-1192. Epub 2021 Jan 29 doi: 10.1038/s41430-020-00841-x. PMID: 33514872
Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.
Paz MFCJ, de Alencar MVOB, de Lima RMP, Sobral ALP, do Nascimento GTM, Dos Reis CA, Coêlho MDPSS, do Nascimento MLLB, Gomes Júnior AL, Machado KDC, de Menezes APM, de Lima RMT, de Oliveira Filho JWG, Dias ACS, Dos Reis AC, da Mata AMOF, Machado SA, Sousa CDC, da Silva FCC, Islam MT, de Castro E Sousa JM, Melo Cavalcante AAC
Oxid Med Cell Longev 2020;2020:3457890. Epub 2020 Mar 28 doi: 10.1155/2020/3457890. PMID: 32308801Free PMC Article
Potential Clinical Applications of Stem Cells in Regenerative Medicine.
Suman S, Domingues A, Ratajczak J, Ratajczak MZ
Adv Exp Med Biol 2019;1201:1-22. doi: 10.1007/978-3-030-31206-0_1. PMID: 31898779
The hallmarks of aging.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G
Cell 2013 Jun 6;153(6):1194-217. doi: 10.1016/j.cell.2013.05.039. PMID: 23746838Free PMC Article

Diagnosis

Helicobacter pylori and Gastric Cancer: Pathogenetic Mechanisms.
Salvatori S, Marafini I, Laudisi F, Monteleone G, Stolfi C
Int J Mol Sci 2023 Feb 2;24(3) doi: 10.3390/ijms24032895. PMID: 36769214Free PMC Article
PARP and PARG inhibitors in cancer treatment.
Slade D
Genes Dev 2020 Mar 1;34(5-6):360-394. Epub 2020 Feb 6 doi: 10.1101/gad.334516.119. PMID: 32029455Free PMC Article
Mechanisms of Genomic Instability in Breast Cancer.
Duijf PHG, Nanayakkara D, Nones K, Srihari S, Kalimutho M, Khanna KK
Trends Mol Med 2019 Jul;25(7):595-611. Epub 2019 May 8 doi: 10.1016/j.molmed.2019.04.004. PMID: 31078431
Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease.
Donato AJ, Machin DR, Lesniewski LA
Circ Res 2018 Sep 14;123(7):825-848. doi: 10.1161/CIRCRESAHA.118.312563. PMID: 30355078Free PMC Article
Werner syndrome: Clinical features, pathogenesis and potential therapeutic interventions.
Oshima J, Sidorova JM, Monnat RJ Jr
Ageing Res Rev 2017 Jan;33:105-114. Epub 2016 Mar 15 doi: 10.1016/j.arr.2016.03.002. PMID: 26993153Free PMC Article

Therapy

Targeting replication stress in cancer therapy.
da Costa AABA, Chowdhury D, Shapiro GI, D'Andrea AD, Konstantinopoulos PA
Nat Rev Drug Discov 2023 Jan;22(1):38-58. Epub 2022 Oct 6 doi: 10.1038/s41573-022-00558-5. PMID: 36202931
Understanding and overcoming resistance to PARP inhibitors in cancer therapy.
Dias MP, Moser SC, Ganesan S, Jonkers J
Nat Rev Clin Oncol 2021 Dec;18(12):773-791. Epub 2021 Jul 20 doi: 10.1038/s41571-021-00532-x. PMID: 34285417
PARP and PARG inhibitors in cancer treatment.
Slade D
Genes Dev 2020 Mar 1;34(5-6):360-394. Epub 2020 Feb 6 doi: 10.1101/gad.334516.119. PMID: 32029455Free PMC Article
Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future.
McGranahan N, Swanton C
Cell 2017 Feb 9;168(4):613-628. doi: 10.1016/j.cell.2017.01.018. PMID: 28187284
Targeting the DNA Damage Response in Cancer.
O'Connor MJ
Mol Cell 2015 Nov 19;60(4):547-60. doi: 10.1016/j.molcel.2015.10.040. PMID: 26590714

Prognosis

Epigenetics, DNA damage, and aging.
Soto-Palma C, Niedernhofer LJ, Faulk CD, Dong X
J Clin Invest 2022 Aug 15;132(16) doi: 10.1172/JCI158446. PMID: 35968782Free PMC Article
PARP and PARG inhibitors in cancer treatment.
Slade D
Genes Dev 2020 Mar 1;34(5-6):360-394. Epub 2020 Feb 6 doi: 10.1101/gad.334516.119. PMID: 32029455Free PMC Article
DNA Damage and Repair Biomarkers of Immunotherapy Response.
Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD
Cancer Discov 2017 Jul;7(7):675-693. Epub 2017 Jun 19 doi: 10.1158/2159-8290.CD-17-0226. PMID: 28630051Free PMC Article
Molecular and biological hallmarks of ageing.
Aunan JR, Watson MM, Hagland HR, Søreide K
Br J Surg 2016 Jan;103(2):e29-46. doi: 10.1002/bjs.10053. PMID: 26771470
Genomic instability--an evolving hallmark of cancer.
Negrini S, Gorgoulis VG, Halazonetis TD
Nat Rev Mol Cell Biol 2010 Mar;11(3):220-8. doi: 10.1038/nrm2858. PMID: 20177397

Clinical prediction guides

CXCL10 potentiates immune checkpoint blockade therapy in homologous recombination-deficient tumors.
Shi Z, Shen J, Qiu J, Zhao Q, Hua K, Wang H
Theranostics 2021;11(15):7175-7187. Epub 2021 May 24 doi: 10.7150/thno.59056. PMID: 34158843Free PMC Article
PARP and PARG inhibitors in cancer treatment.
Slade D
Genes Dev 2020 Mar 1;34(5-6):360-394. Epub 2020 Feb 6 doi: 10.1101/gad.334516.119. PMID: 32029455Free PMC Article
DNA Damage and Repair Biomarkers of Immunotherapy Response.
Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD
Cancer Discov 2017 Jul;7(7):675-693. Epub 2017 Jun 19 doi: 10.1158/2159-8290.CD-17-0226. PMID: 28630051Free PMC Article
DNA replication stress as a hallmark of cancer.
Macheret M, Halazonetis TD
Annu Rev Pathol 2015;10:425-48. doi: 10.1146/annurev-pathol-012414-040424. PMID: 25621662
Genomic instability--an evolving hallmark of cancer.
Negrini S, Gorgoulis VG, Halazonetis TD
Nat Rev Mol Cell Biol 2010 Mar;11(3):220-8. doi: 10.1038/nrm2858. PMID: 20177397

Recent systematic reviews

ESMO recommendations on predictive biomarker testing for homologous recombination deficiency and PARP inhibitor benefit in ovarian cancer.
Miller RE, Leary A, Scott CL, Serra V, Lord CJ, Bowtell D, Chang DK, Garsed DW, Jonkers J, Ledermann JA, Nik-Zainal S, Ray-Coquard I, Shah SP, Matias-Guiu X, Swisher EM, Yates LR
Ann Oncol 2020 Dec;31(12):1606-1622. Epub 2020 Sep 28 doi: 10.1016/j.annonc.2020.08.2102. PMID: 33004253
PARP Inhibitors in the Management of Ovarian Cancer: ASCO Guideline.
Tew WP, Lacchetti C, Ellis A, Maxian K, Banerjee S, Bookman M, Jones MB, Lee JM, Lheureux S, Liu JF, Moore KN, Muller C, Rodriguez P, Walsh C, Westin SN, Kohn EC
J Clin Oncol 2020 Oct 20;38(30):3468-3493. Epub 2020 Aug 13 doi: 10.1200/JCO.20.01924. PMID: 32790492Free PMC Article
Potential genetic causes of miscarriage in euploid pregnancies: a systematic review.
Colley E, Hamilton S, Smith P, Morgan NV, Coomarasamy A, Allen S
Hum Reprod Update 2019 Jul 1;25(4):452-472. doi: 10.1093/humupd/dmz015. PMID: 31150545
Oxidative stress, genomic features and DNA repair in frail elderly: A systematic review.
Sánchez-Flores M, Marcos-Pérez D, Costa S, Teixeira JP, Bonassi S, Pásaro E, Laffon B, Valdiglesias V
Ageing Res Rev 2017 Aug;37:1-15. Epub 2017 May 6 doi: 10.1016/j.arr.2017.05.001. PMID: 28487242
The emerging roles of Jab1/CSN5 in cancer.
Wang L, Zheng JN, Pei DS
Med Oncol 2016 Aug;33(8):90. Epub 2016 Jul 13 doi: 10.1007/s12032-016-0805-1. PMID: 27412572

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