Genomic instability — an evolving hallmark of cancer

By Simona Negrini, Vassilis G. Gorgoulis, T. Halazonetis. Nature reviews. Molecular cell biology, 2010

2,285 citations recorded by the source corpus.

Genomic instability is a characteristic of most cancers. In hereditary cancers, genomic instability results from mutations in DNA repair genes and drives cancer development, as predicted by the mutator hypothesis. In sporadic (non-hereditary) cancers the molecular basis of genomic instability remains unclear, but recent high-throughput sequencing studies suggest that mutations in DNA repair genes are infrequent before therapy, arguing against the mutator hypothesis for these cancers. Instead, the mutation patterns of the tumour suppressor TP53 (which encodes p53), ataxia telangiectasia mutated (ATM) and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF) support the oncogene-induced DNA replication stress model, which attributes genomic instability and TP53 and ATM mutations to oncogene-induced DNA damage.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/d650b832e9bc4c4463c08bce14b027129d2a083c

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Citations in the corpus

DNA replication stress as a hallmark of cancer. (2015, background): “We have argued in the past that these two hallmarks are in fact two sides of the same coin (26).”
Hallmarks of cancer: the next generation. (2011, positive): “The catalog of defects in these caretaker genes includes those whose products are involved in (1) detecting DNA damage and activating the repair machinery, (2) directly repairing damaged DNA, and (3) inactivating or intercepting mutagenic molecules before they have damaged the DNA (Negrini et al., 2”
Apoptosis and Molecular Targeting Therapy in Cancer (2014, background): “Under many stressful conditions like precancerous lesions, activation of the DNA damage checkpoint pathway can serve to remove potentially harmful DNA-damaged cells via apoptosis induction to block carcinogenesis [4, 5].”
Mechanisms and insights into drug resistance in cancer (2013, background): “Nesse, R. M. (2001). How is Darwinian medicine useful? West.”
The DNA Damage Response: Making it safe to play with knives (2010, background): “Other forms of genomic instability include accumulation of DNA basemutations andmicrosatellite instability (MIN), which results in contraction or expansion of the number of repetitive microsatellite sequences (Negrini et al., 2010).”
Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. (2011, background): “Chromosomal instability leads to altered gene dosage and the potential for a cell to rapidly evolve and mutate, due to its genetic plasticity, into diverse abnormal genotypes that can escape the homeostatic control mechanisms and thus become immortalised and evade the immune system (70,71).”
Targeting p53 pathways: mechanisms, structures and advances in therapy (2023, background): “Significant upregulation of proteins associated with cell cycle progression was also observed in p53 mutant cancers, which may be due to loss of control of cell cycle checkpoints by TP53 deletion.(225,229,230) Scott W.”
DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy (2021, background): “Genomic instability is a common characteristic of most cancer cells.(68) For example, a high ratio of chromosomal instability is associated with mitotic spindle checkpoint deficiency in most breast cancer cell lines.”
Strategies to improve radiotherapy with targeted drugs (2011, background): “In addition, many cancers in patients without such germline mutations have an impaired DDR and defective checkpoints, as exemplified by the high incidence of ATM , TP53 (which encodes p53) and cyclin-dependent kinase inhibitor 2A ( CDKN2A ) mutation”
Genome-Wide Detection of Single Nucleotide and Copy Number Variations of a Single Human Cell (2012, background): “The variations occurring in these chromosomes, such as single nucleotide variations (SNVs) and copy number variations (CNVs) (3), are the driving forces in biological processes such as evolution and cancer.”
Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis (2010, positive): “The importance of DNA repair is evident, as deficiencies in several repair pathways are associated with human diseases, including cance”