China
Africa
Explore chapters and articles related to this topic
Forensic Genetics and Genomic
Published in Cristoforo Pomara, Vittorio Fineschi, Forensic and Clinical Forensic Autopsy, 2020
Francesco Sessa, Francesca Maglietta, Alessio Asmundo, Cristoforo Pomara
The human genome is organized as 23 pairs of chromosomes: the X and Y sex chromosomes and the remaining autosomal chromosome pairs, numbered 1–22. The human genome is peppered with regions of repetitive DNA – hypervariable regions consisting of a short DNA sequence repeated in tandem. These regions are polymorphic in that the sequence varies in the number of copies of the repeat unit. The number of repeat units is indicated by the allele designation (Anderson et al., 1981).
Colon cancer: pathology and natural history
Published in A. R. Genazzani, 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+).
Acute and Chronic Transforming Retroviruses
Published in Pimentel Enrique, Oncogenes, 2020
Although transposable genetic elements similar to those described in yeast and insects have not been rigorously identified in mammals, a family of middle repetitive DNA elements described in the mouse may have similar or identical function.152 These mouse elements show characteristics of both insertion sequences (ISs) and solitary retroviral LTRs, and have been termed LTR-IS. They are about 500 bp in length, have 11 bp inverted repeats at their termini and contain regulatory signals implicated in transcription by RNA polymerase II. There are about 500 LTR-IS per mouse haploid genome, interspersed among variable flanking regions of mouse DNA, and their structure suggests that they could be mobile in the genome and function as insertion mutagens. However, LTR-IS elements seem to be relatively stable within the genome. If LTR-IS elements are mobile, they do not rearrange frequently or may have lost their mobility during evolution. Consequently, LTR-IS may represent an evolutionary intermediate in retroviral evolution. The possible role of LTR-IS and other repetitive DNA sequences, like the human Alu sequences, in normal developmental processes and/or oncogenic processes in only beginning to be understood.153-157
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).
An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer
Published in Expert Review of Clinical Pharmacology, 2020
Jeffrey A. Rappaport, Scott A. Waldman
Less frequently (<15%), colon tumors arise through the microsatellite instability pathway (MSI), defined by loss of DNA mismatch repair proteins, most commonly MLH1 or MSH2 [23,31]. Their loss disrupts normal DNA repair, permitting the accumulation of mutations in short, repetitive DNA sequences called microsatellite sequences. These frequent DNA base pair mutations phenotypically distinguish MSI from CIN tumors, and contribute to a more rapid tumor progression (1–3 years, vs. 10 or more years for CIN tumors) [34]. MSI tumors also exhibit aberrant methylation of key DNA regulatory regions, described as the CpG island methylator phenotype (CIMP), producing epigenetic silencing of key tumor suppressor genes. MLH1 promoter methylation represents the most common driver of the MSI phenotype. Although most MSI tumors arise sporadically, the most common hereditary colon cancer syndrome, hereditary non-polyposis colorectal cancer (HNPCC, or Lynch syndrome), arises from germline mutations in MLH1 or MSH2.
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.