Microsatellite instability in colorectal cancer

By M. Horvat, B. Štabuc. Radiology and Oncology, 2011

1,396 citations recorded by the source corpus.

Microsatellite instability in colorectal cancer Background. Colorectal cancer (CRC) is the third most common cancer in the world. In 75% CRC develops sporadically, in 25% hereditary or as a consequence of inflammatory bowel disease. CRC carcinogenesis develops over many years. The cause of CRC in 85% is chromosomal instability (CIN) and in 15% microsatellite instability (MSI-H), where hereditary nonpolyposis colorectal cancer (HNPCC) represents 10-20%. Microsatellite sequences (MS) are repeated sequences of short stretches of DNA all over the genome. Microsatellite stability (MSS) means MS are the same in each cell of an individual, whereas microsatellite instability (MSI-H) means MS differ in normal and cancer cells of an individual. The cause of MSI-H is a damaged mismatch repair mechanism (MMR), with the most important MMR proteins being MSH2, MLH1 and MSH6. Conclusions. MSI-H seems to be an important prognostic factor in CRC and an important predictive factor of CRC chemotherapeutic treatment efficacy. Clinical trials conducted until now have shown contradictory findings in different chemotherapeutic settings, adjuvant and palliative; therefore MSI-H is going to be the object of the future research. The future of cancer treatment is in the individualized therapy based on molecular characteristics of the tumour, such as MSI-H in CRC.

Subfields: Genetics, Oncology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/e67d044ca5213c0a6bf1e0f5562ba9c7e73af3ee

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Citations in the corpus

Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. (2020, neutral): “Mucosal inflammation 7 (5) 0 27 (19) 1 (1)”
Overexpressed of RAD51 suppresses recombination defects: a possible mechanism to reverse genomic instability (2010, background): “Alternatively, cancers initiated by mutations in genes of the mismatch repair (MMR) pathway and the subsequent microsatellite instability (MSI) are less frequently associated with mutations in TP53 (28,29).”
Microsatellite Instability as a Biomarker for PD-1 Blockade (2016, background): “Further clinical studies have generally substantiated the finding that MSI patients do not benefit from 5FU therapy, with some exceptions (51).”
The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints (2014, neutral): “Through concomitant genetic analysis, we found that this subset of tumors harbored microsatellite instability (MSI), indicating that they were mismatch repair deficient (12).”
Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer (2017, background): “Genes mutated in tumours with microsatellite instability include MLH1 , MSH2 , MSH6 , PMS1 and PMS2 [28].”
deconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution (2016, background): “Exogenous mutagens, such as tobacco smoke and ultraviolet light, and endogenous processes, such as APOBEC enzymatic family functional activity or DNA mismatch repair deficiency, result in characteristic patterns of mutation [1, 2].”
Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. (2021, background): “Tumor samples can be assessed for the sizes of microsatellite markers and classified as MSI high (MSI-H), low (MSI-L), and stable (MSS).(87,90) The NCCN Panel recommends MSI testing and/or MMR testing on available tumor tissue for patients with locally advanced or metastatic pancreatic adenocarcinom”
Prospective derivation of a Living Organoid Biobank of colorectal cancer patients (2015, background): “Mutations of genes in DNA mismatch repair (MMR)-associated pathways are associated with a hypermutated phenotype (Boland and Goel, 2010).”
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency (2015, neutral): “The accumulation of mutations in these regions of the genome is termed microsatellite instability.(26-28) Mismatch-repair status was assessed in tumors with the use of the MSI Analysis System (Promega), through the evaluation of selected microsatellite sequences that are particularly prone to copyin”
Signatures of mutational processes in human cancer (2013, neutral): “Others,forexamplesignatures14,15and21,showoverwhelming activityinasmallnumberofcancercases(SupplementaryFigs38,45 and56,respectively)andareperhapsmorelikelytobeduetocurrently uncharacterized defects in DNA maintenance.”