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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
Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity.
Copland M
Br J Haematol 2022 Dec;199(5):665-678. Epub 2022 Jul 22 doi: 10.1111/bjh.18370. PMID: 35866251Free 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

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
Measuring biological aging in humans: A quest.
Ferrucci L, Gonzalez-Freire M, Fabbri E, Simonsick E, Tanaka T, Moore Z, Salimi S, Sierra F, de Cabo R
Aging Cell 2020 Feb;19(2):e13080. Epub 2019 Dec 12 doi: 10.1111/acel.13080. PMID: 31833194Free 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
Molecular mechanisms in progression of HPV-associated cervical carcinogenesis.
Gupta SM, Mania-Pramanik J
J Biomed Sci 2019 Apr 23;26(1):28. doi: 10.1186/s12929-019-0520-2. PMID: 31014351Free PMC Article
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
Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma.
Dharanipragada P, Zhang X, Liu S, Lomeli SH, Hong A, Wang Y, Yang Z, Lo KZ, Vega-Crespo A, Ribas A, Moschos SJ, Moriceau G, Lo RS
Cancer Discov 2023 Apr 3;13(4):880-909. doi: 10.1158/2159-8290.CD-22-0787. PMID: 36700848Free 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
Tumour heterogeneity and resistance to cancer therapies.
Dagogo-Jack I, Shaw AT
Nat Rev Clin Oncol 2018 Feb;15(2):81-94. Epub 2017 Nov 8 doi: 10.1038/nrclinonc.2017.166. PMID: 29115304
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

Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial.
Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, Nagao S, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alia EM, Bogner G, Yoshida H, Lefeuvre-Plesse C, Buderath P, Mosconi AM, Lortholary A, Burges A, Medioni J, El-Balat A, Rodrigues M, Park-Simon TW, Dubot C, Denschlag D, You B, Pujade-Lauraine E, Harter P; PAOLA-1/ENGOT-ov25 investigators
Ann Oncol 2023 Aug;34(8):681-692. Epub 2023 May 19 doi: 10.1016/j.annonc.2023.05.005. PMID: 37211045
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: 36202931Free PMC Article
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
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

Neuroblastoma arises in early fetal development and its evolutionary duration predicts outcome.
Körber V, Stainczyk SA, Kurilov R, Henrich KO, Hero B, Brors B, Westermann F, Höfer T
Nat Genet 2023 Apr;55(4):619-630. Epub 2023 Mar 27 doi: 10.1038/s41588-023-01332-y. PMID: 36973454Free PMC Article
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
Metagenomic next-generation sequencing to identify pathogens and cancer in lung biopsy tissue.
Guo Y, Li H, Chen H, Li Z, Ding W, Wang J, Yin Y, Jin L, Sun S, Jing C, Wang H
EBioMedicine 2021 Nov;73:103639. Epub 2021 Oct 23 doi: 10.1016/j.ebiom.2021.103639. PMID: 34700283Free 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
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

Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial.
Pujade-Lauraine E, Brown J, Barnicle A, Wessen J, Lao-Sirieix P, Criscione SW, du Bois A, Lorusso D, Romero I, Petru E, Yoshida H, Vergote I, Colombo N, Hietanen S, Provansal M, Schmalfeldt B, Pignata S, Martín Lorente C, Berton D, Runnebaum IB, Ray-Coquard I
JCO Precis Oncol 2023 Jan;7:e2200258. doi: 10.1200/PO.22.00258. PMID: 36716415Free 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
Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer.
Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, Szallasi Z, Barry WT, Winer EP, Tung NM, Isakoff SJ, Ryan PD, Greene-Colozzi A, Gutin A, Sangale Z, Iliev D, Neff C, Abkevich V, Jones JT, Lanchbury JS, Hartman AR, Garber JE, Ford JM, Silver DP, Richardson AL
Clin Cancer Res 2016 Aug 1;22(15):3764-73. Epub 2016 Mar 8 doi: 10.1158/1078-0432.CCR-15-2477. PMID: 26957554Free 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

Synthetic lethal mutants in Escherichia coli define pathways necessary for survival with RNase H deficiency.
Das S, Forrest J, Kuzminov A
J Bacteriol 2023 Oct 26;205(10):e0028023. Epub 2023 Oct 11 doi: 10.1128/jb.00280-23. PMID: 37819120Free PMC Article
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
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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