Colon cancer: pathology and natural history
A. R. Genazzani in Hormone Replacement Therapy and Cancer, 2020
Recognition of the role of defective MMR in HNPCC has been gready facilitated by recognition that tumors defective in MMR demonstrate the associated phenotype of instability of micro-satellite (MSI) DNA sequences. DNA microsatellites are regions of repetitive DNA sequences in which the repeated unit is from one to three DNA bases long. The most common class of such microsatellites is of the form (CA)n. Such microsatellite repeats are scattered throughout the human genome. DNA polymerases are prone to slip while copying long stretches of these repetitive DNA sequences; thus, in the absence of effective DNA MMR, the resulting insertion or deletion errors are undetected and unrepaired. Tumors that demonstrate such MSI are alternatively referred to as tumors that demonstrate replication errors (RER+).
Nodulin Function and Nodulin Gene Regulation in Root Nodule Development
Peter M. Gresshoff in Molecular Biology of Symbiotic Nitrogen Fixation, 2018
The soybean n-uricase gene encompasses almost 5000 base pairs (bp). It has seven introns, ranging in size from 154 to 1341 bp.98 The gene coding for Ngm-24 has four introns.131 The structure of the Ngm-24 gene is rather unusual. It contains three almost identical exons. Both the 5' and 3' intron sequences flanking these exons are conserved, and two of the introns are also almost identical. As a result, the Ngm-24 gene contains three direct repeats arranged in tandem in the center of its DNA sequence. The repeated sequence has the characteristics of an insertion element that may have been used in evolution to generate genes via duplication.131 The genes for the three peribacteroid membrane nodulins Ngm-23, Ngm-20, and Ngm-27 all have one intron which separates a small exon of 7 to 15 amino acids at the carboxy terminal end from the rest of the coding sequence.134,150 The homologies found between these nodulin genes extend to the 3' noncoding region, suggesting that the genes encoding peribacteroid membrane nodulins have only recently been derived from a common ancestor.
The Structure of Transcriptons and The Regulation of Transcription
M. Gerald, M.D. Kolodny in Eukaryotic Gene Regulation, 2018
Much progress has also been obtained in studies on repetitive DNA (sections IV-V). In particular, certain short (100 to 200 b.p.) interspersed transcribed DNA sequences were found to be scattered throughout the whole eykaryotic genome.205,206 For example, in mouse the sequences Bl and B2 are repeated from 104 to 105 times and penetrate the whole genome. Most of dsRNA-B is transcribed from these two sequences. They have been sequenced and found to contain regions homologous to the regions of exon-intron and intron-exon junctions and to the origins of replication of papova viruses.207,208 The data support the ideas on involvement of dsRNA-B coding sequences in processing.
The fractal dimension of chromatin - a potential molecular marker for carcinogenesis, tumor progression and prognosis
Published in Expert Review of Molecular Diagnostics, 2019
Konradin Metze, Randall Adam, João Batista Florindo
In summary, fractality is simultaneously present at different levels of nuclear organization. Now, we have to ask, whether all these levels are interrelated, for instance, whether a fractal arrangement of the DNA base sequence could lead to the emergence of a 3D fractal structure of chromatin. One hypothesis suggests that this might be due to the fractal features of fluctuating proportions of nucleotide bases [76]. Other authors discuss the possibility that ‘repeat pair interactions’ might provoke clusters in the 3D chromatin space, thus modulating higher order structures. Since repetitive DNA elements are considered to coordinate chromatin folding [95] and since repetitive DNA sequences from transposable elements are distributed according to power laws for inter repeat distances [96], we may deduce that the fractal organization of the DNA sequence probably contributes to the emergence of the 3D fractal structure [79].
Microsatellite instability and oncological outcomes in Thai patients with endometrial cancer
Published in Journal of Obstetrics and Gynaecology, 2022
Thiti Atjimakul, Panote Wattanapaisal, Supaporn Suwiwat, Worrawit Wanichsuwan, Jitti Hanprasertpong
Endometrial cancer (EC) was included as a common gynaecological cancer in the Global Cancer Statistics report in 2020; over 417,367 new cases were reported in 2020 (Sung et al. 2021). The National Cancer Institute of Thailand has also reported EC as the third most common gynaecological cancer in the Thai female population, with three per 100,000 cases per year (Virani et al. 2017). Most ECs occur sporadically, with only 3–5% being related to germline mutation (Thibodeau et al. 1993; Herman et al. 1998; Boland et al. 2008). Genetic alterations in EC are frequently associated with the loss of mismatch repair (MMR) system. The latter involves a repetitive DNA sequence-repair mechanism that maintains genomic integrity by correcting base substitutions and minor insertion–deletion mismatches generated due to base-pairing errors by DNA polymerase during replication. Mutations in MMR genes, such as mutL homolog 1 (MLH1); mutS homologs 6 (MSH6), 2 (MSH2) and 3 (MSH3); and PMS1 homolog 2 (PMS2), assemble as microsatellite sequences throughout the genome, a phenomenon realised as microsatellite instability (MSI) (Lower et al. 2018).
British Journal of Biomedical Science in 2020. What have we learned?
Published in British Journal of Biomedical Science, 2020
The genome contains areas of DNA termed microsatellites which are sequences of repetitive DNA units, which can lead to errors in the DNA mismatch repair system. This leads to microsatellite instability (MSI) which can be detected in the DNA of peripheral cells. This screening is used in detecting Lynch syndrome, where there is a 50–70% lifetime risk of developing colorectal cancer, and a 40–60% risk of developing endometrial and other malignancies [56]. Issue 3 opened with a report from Sanchez and colleagues [57] examined a MSI in the Caspase 2 gene (CAT25), BAT 25 which occurs in the c-kit and BAT26 located in hMSH2. The authors showed CAT25 analysis to be fast as it can use high-resolution PCR rather than the usual capillary electrophoresis and has a 100% predictive value for a tumour having high MSI.
Related Knowledge Centers
- Centromere
- Chromosomal Crossover
- Genome
- Genomic DNA
- Microsatellite
- Minisatellite
- Nucleic Acid
- Tandem Repeat
- Telomere
- Interspersed Repeat