Microsatellite instability, MLH-1 promoter hypermethylation, and frameshift mutations at coding mononucleotide repeat microsatellites in ovarian tumors

Mutations in the DNA mismatch repair (MMR) system lead to an instability of simple repetitive DNA sequences involved in several cancer types. This instability is reflected in a high mutation rate of microsatellites, and recent studies in colon cancer indicate that defects in MMR result in frequent frameshift mutations in mononucleotide repeats located in the coding regions of BAX and transforming growth factor-β (TGF-β) receptor genes. Circumstantial evidence suggests that the MMR defect may be involved in some lymphoid malignancies, although several allelotype analyses have concluded on the low level of microsatellite instability in acute lymphoblastic leukemias. To further evaluate the implication of MMR defects in leukemogenesis, we have studied a series of 98 children with acute lymphoblastic leukemia and 14 leukemic cell lines using several indicators of MMR defects. Microsatellite markers were compared between blast and normal DNA from the same patients and mutations were sought in mononucleotide repeat sequences of BAX and TGF-β receptor II (TGF-β RII). The absence of microsatellite instability (MI) and the absence of mutations in the genes examined from patient's leukemic cells contrasted with the observation that half of the cell lines displayed a high degree of MI and that three of seven of these mutator cell lines harbored mutations in BAX and/or TGF-β RII. From these results we conclude that MMR defects are very uncommon in freshly isolated blasts but are likely to be selected for during the establishment of cell lines.

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Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability

Cancer ◽

10.1002/(sici)1097-0142(20000515)88:10<2290::aid-cncr13>3.0.co;2-i ◽

2000 ◽

Vol 88 (10) ◽

pp. 2290-2297 ◽

Cited By ~ 23

Author(s):

Lluis Catasus ◽

Xavier Matias-Guiu ◽

Pilar Machin ◽

Gian Franco Zannoni ◽

Giovanni Scambia ◽

...

Keyword(s):

Microsatellite Instability ◽

Endometrial Carcinoma ◽

Mononucleotide Repeat ◽

Frameshift Mutations

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Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer

World Journal of Gastroenterology ◽

10.3748/wjg.v13.i12.1767 ◽

2007 ◽

Vol 13 (12) ◽

pp. 1867 ◽

Cited By ~ 24

Author(s):

Yaron Niv

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Promoter Hypermethylation ◽

Mlh1 Promoter

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Serrated Polyps and Serrated Polyposis Syndrome

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0036-1584088 ◽

2016 ◽

Vol 29 (04) ◽

pp. 336-344 ◽

Cited By ~ 5

Author(s):

Jean Ashburn ◽

Thomas Plesec ◽

Matthew Kalady

Keyword(s):

Microsatellite Instability ◽

Clinical Management ◽

Promoter Hypermethylation ◽

Colorectal Cancers ◽

Polyposis Syndrome ◽

Management Guidelines ◽

Serrated Polyps

AbstractColorectal serrated polyps are intermediate lesions in the serrated neoplastic pathway, which account for up to 30% of colorectal cancers. This pathway is biologically distinct from the adenoma-to-carcinoma sequence, with associated cancers exhibiting mutations in the BRAF oncogene, DNA promoter hypermethylation, and microsatellite instability. An evolving understanding of these unique lesions has led to the development of a more accurate classification, improved endoscopic identification, and tailored clinical management guidelines. This article reviews serrated polyps and serrated polyposis syndrome.

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