Instabilidade de microssatélite - MSI nos marcadores (BAT26, BAT25, D2s123, D5S346, D17S250) no câncer de reto

Losso, Graziele Moraes; Moraes, Roberto da Silveira; Gentili, Arthur Conelian; Messias-Reason, Iara

doi:10.1590/s0102-67202012000400006

Cited by 23 publications

(11 citation statements)

References 20 publications

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“…MSI can be considered a promising prognostic marker for CRC patients and MSI status can be assessed through a panel of five markers ( BAT25 , BAT26 , D2S123 , D5S346 , and D17S2720 ) and the use of polymerase chain reaction (PCR). MSI-high is characterized by instability at two loci or more, and MSI-Low by instability at one locus[39]. Currently, the main clinical use of MSI testing is to detect patients with Lynch syndrome.…”

Section: Tissue- Based Biomarkersmentioning

confidence: 99%

Biomarkers in colorectal cancer: Current clinical utility and future perspectives

Vacante

Borzì

Burzotta

et al. 2018

WJCC

106

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Colorectal cancer (CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a sporadic disease in most cases (75%-80%), but it has been suggested that crosstalk between gene mutations (i.e., mutations of BRAF, KRAS, and p53 as well as microsatellite instability) and epigenetic alterations (i.e., DNA methylation of CpG island promoter regions) could play a pivotal role in cancer development. A number of studies have focused on molecular testing to guide targeted and conventional treatments for patients with CRC, sometimes with contrasting results. Some of the most useful innovations in the management of CRC include the possibility to detect the absence of KRAS, BRAF, NRAS and PIK3CA gene mutations with the subsequent choice to administer targeted adjuvant therapy with anti-epidermal growth factor receptor antibodies. Moreover, CRC patients can benefit from tests for microsatellite instability and for the detection of loss of heterozygosity of chromosome 18q that can be helpful in guiding therapeutic decisions as regards the administration of 5-FU. The aim of this review was to summarize the most recent evidence on the possible use of genetic or epigenetic biomarkers for diagnosis, prognosis and response to therapy in CRC patients.

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Section: Tissue- Based Biomarkersmentioning

confidence: 99%

Biomarkers in colorectal cancer: Current clinical utility and future perspectives

Vacante

Borzì

Burzotta

et al. 2018

WJCC

106

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“…Liengswangwong et al reported MSI-low and MSS in liver fluke infection-associated intrahepatic CCA (34). In addition, the prognostic and predictive impacts of MSI status in patients with colon cancer have been reported (35,36). Previously, it was demonstrated the generation of a mutator phenotype in yeast was caused by imbalanced BER (37).…”

Section: Discussionmentioning

confidence: 99%

Imbalanced adaptive responses associated with microsatellite instability in cholangiocarcinoma

et al. 2016

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The adaptive response of the genome protection mechanism occurs in cells when exposed to genotoxic stress due to the overproduction of free radicals via inflammation and infection. In such circumstances, cells attempt to maintain health via several genome protection mechanisms. However, evidence is increasing that this adaptive response may have deleterious effect; a reduction of antioxidant enzymes and/or imbalance in the DNA repair system generates microsatellite instability (MSI), which has procarcinogenic implications. Therefore, the present study hypothesized that MSI caused by imbalanced responses of antioxidant enzymes and/or DNA repair enzymes as a result of oxidative/nitrative stress arising from the inflammatory response is involved in liver fluke-associated cholangiocarcinogenesis. The present study investigated this hypothesis by identifying the expression patterns of antioxidant enzymes, including superoxide dismutase 2 (SOD2) and catalase (CAT), and DNA repair enzymes, including alkyladenine DNA glycosylase (AAG), apurinic endonuclease (APE) and DNA polymerase β (DNA pol β). In addition, the activities of the antioxidant enzymes, SOD2 and CAT, were examined in human cholangiocarcinoma (CCA) tissues using immunohistochemical staining. MSI was also analyzed in human CCA tissues. The resulting data demonstrated that the expression levels of the SOD2 and CAT enzymes decreased. The activities of SOD2 and CAT decreased significantly in the CCA tissues, compared with the hepatic tissue of cadaveric donors. In the DNA repairing enzymes, it was found that the expression levels of AAG and DNA pol β enzymes increased, whereas the expression of APE decreased. In addition, it was found that MSI-high was present in 69% of patients, whereas MSI-low was present in 31% of patients, with no patients classified as having microsatellite stability. In the patients, a MSI-high was correlated with poor prognosis, indicated by a shorter survival rate. These results indicated that the reduction of antioxidant enzymes and adaptive imbalance of base excision repair enzymes in human CCA caused MSI, and may be associated with the progression of cancer.

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“…The identification process is based on analyzing the difference in the length of microsatellite repeats in tumor tissue compared to the healthy non-neoplastic tissue surrounding the tumor. Generally, panels of 10 markers [ 67 ] and commercially available kits [ 68 , 69 ] are in use, as well as a panel proposed by Bethesda [ 7 , 70 , 71 ].…”

Section: Diagnostics Of Lsmentioning

confidence: 99%

Diagnostics of Mutations in MMR/EPCAM Genes and Their Role in the Treatment and Care of Patients with Lynch Syndrome

et al. 2020

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Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a disorder caused by an autosomal dominant heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. Individuals with LS are at an increased risk of developing colorectal and extracolonic cancers, such as endometrial, small bowel, or ovarian. In this review, the mutations involved with LS and their diagnostic methods are described and compared, as are their current uses in clinical decision making. Nowadays, LS diagnosis is based on a review of family medical history, and when necessary, microsatellite instability (MSI) or/and immunohistochemistry (IHC) analyses should be performed. In the case of a lack of MMR protein expression (dMMR) or MSI-H (MSI-High) detection in tumor tissue, molecular genetic testing can be undertaken. More and more genetic testing for LS is based mainly on next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA), which provide better and quicker information about the molecular profile of patients as well as individuals at risk. Testing based on these two methods should be the standard and commonly used. The identification of individuals with mutations provides opportunities for the detection of cancer at an early stage as well as the introduction of proper, more effective treatment, which will result in increased patient survival and reduced costs of medical care.

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Instabilidade de microssatélite - MSI nos marcadores (BAT26, BAT25, D2s123, D5S346, D17S250) no câncer de reto

Cited by 23 publications

References 20 publications

Biomarkers in colorectal cancer: Current clinical utility and future perspectives

Biomarkers in colorectal cancer: Current clinical utility and future perspectives

Imbalanced adaptive responses associated with microsatellite instability in cholangiocarcinoma

Diagnostics of Mutations in MMR/EPCAM Genes and Their Role in the Treatment and Care of Patients with Lynch Syndrome

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