Mismatch repair, p53 and chromosomal aberrations in primary colorectal carcinomas

Mehigan, Brian; Ashman, J. N. E.; Baker, Richard P.; Macdonald, Alastair A.; Greenman, John; Monson, J. R. T.; Cawkwell, Lynn

doi:10.1080/02841860500374463

Cited by 2 publications

(2 citation statements)

References 20 publications

(24 reference statements)

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“…Mehigan et al observed, in tumors with microsatellite stability (MMR-proficient), that p53 did not influence the total number of chromosomal aberrations. The decreased chromosomal aberrations were associated with the loss of hMLH1 or hMSH2 protein expressions, while p53 overexpression was not proven [54]. MMR and p53 were able to cooperate in modulating the sensitivity of the MMR-defective CRC cell line to cisplatin [55] (Table 1).…”

Section: Dna Damage Dna Repair and Tp53mentioning

confidence: 99%

The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

Vodička

Anděra

Opattová

et al. 2021

Cancers

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The disruption of genomic integrity due to the accumulation of various kinds of DNA damage, deficient DNA repair capacity, and telomere shortening constitute the hallmarks of malignant diseases. DNA damage response (DDR) is a signaling network to process DNA damage with importance for both cancer development and chemotherapy outcome. DDR represents the complex events that detect DNA lesions and activate signaling networks (cell cycle checkpoint induction, DNA repair, and induction of cell death). TP53, the guardian of the genome, governs the cell response, resulting in cell cycle arrest, DNA damage repair, apoptosis, and senescence. The mutational status of TP53 has an impact on DDR, and somatic mutations in this gene represent one of the critical events in human carcinogenesis. Telomere dysfunction in cells that lack p53-mediated surveillance of genomic integrity along with the involvement of DNA repair in telomeric DNA regions leads to genomic instability. While the role of individual players (DDR, telomere homeostasis, and TP53) in human cancers has attracted attention for some time, there is insufficient understanding of the interactions between these pathways. Since solid cancer is a complex and multifactorial disease with considerable inter- and intra-tumor heterogeneity, we mainly dedicated this review to the interactions of DNA repair, telomere homeostasis, and TP53 mutational status, in relation to (a) cancer risk, (b) cancer progression, and (c) cancer therapy.

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Section: Dna Damage Dna Repair and Tp53mentioning

confidence: 99%

The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

Vodička

Anděra

Opattová

et al. 2021

Cancers

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“…Thus, it is now well established that the development and progression of CRC are associated with an accumulation of chromosomal abnormalities involving key regulatory genes in normal colonic mucosal cells 3–6. Among other abnormalities, CRC has been associated with mutations involving (i) the adenomatous polyposis coli ( APC ) gene, which is thought to occur early on during the development of adenomatous polyps; (ii) activation of the RAS oncogene (during the adenomatous stage); and (iii) concurrent deletion of multiple chromosomal regions in the transition to carcinoma (ie those involving chromosomes 17p and 18q, which contain the TP53 and DCC genes, respectively), in addition to genes involved in DNA repair 7–11. In contrast, chromosomal abnormalities involved in determining disease progression to a metastatic tumour remain largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis

Sayagués

Abad

Melchor

et al. 2010

The Journal of Pathology

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Much has been learned about the chromosomal abnormalities of colorectal carcinomas but the cytogenetic relationship between the neoplastic clones present in primary versus metastatic tumour samples remains unclear. We analyse the frequency of abnormalities for 47 chromosome regions using the interphase fluorescence in situ hybridization technique in a group of 48 tumours, including 24 primary colorectal tumours and 24 paired liver metastases. All tumours showed complex karyotypes with numerical/structural abnormalities for seven or more different chromosomes/chromosome regions both in the primary tumours and in their paired metastases. Chromosome 8 was the most frequently altered (22/24 primary tumours), consistently showing del(8p22) and/or gains/amplification of 8q24, followed by abnormalities of the entire chromosome 7 (21/24 primary tumours) and of chromosomes 17p and 20q (20/24 primary tumours). Simultaneous staining for multiple chromosome probes revealed the presence of two or more tumour cell clones in 23/24 cases (46/48 tumour samples). Interestingly, the liver metastases typically contained tumour cell clones similar to those found in the primary tumours, suggesting the absence of selective selection of specific tumour clones. Despite this, additional chromosomal abnormalities were detected in 23/24 metastatic tumours, which preferentially consisted of del(17p13) and gains/amplification of 11q13 and 20q13; moreover, compared to primary tumours, metastases showed an increased number of abnormalities of chromosomes 1p, 7q, 8q, 13q, and 18q, and new chromosomal abnormalities involving chromosomes 6, 10q23, 14q32, 15q22, and 19q13. Owing to the high frequency of numerical abnormalities of the entire chromosome 7 and loss and/or gain/amplification of specific regions of chromosome 8, eg del(8p22) and/or gains/amplification of 8q24 in primary colorectal tumours with associated metastases, it is suggested that their assessment at diagnosis could be of great clinical utility for the identification of colorectal cancer patients at higher risk of developing liver metastases.

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Mismatch repair, p53 and chromosomal aberrations in primary colorectal carcinomas

Cited by 2 publications

References 20 publications

The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

The Interactions of DNA Repair, Telomere Homeostasis, and p53 Mutational Status in Solid Cancers: Risk, Prognosis, and Prediction

Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis

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