PMID: 8960367Nov 1, 1996Paper

Cancer of the microsatellite mutator phenotype

Biological Chemistry
M Perucho

Abstract

This review focuses on the genomic instability underlying the microsatellite mutator phenotype (MMP) pathway for cancer. MMP was discovered by the application of DNA fingerprinting by Arbitrarily Primed PCR (AP-PCR) to the analysis of somatic genetic alterations in colon tumors. The unbiased nature of AP-PCR permitted to infer, from the mobility shifts observed in some fingerprint bands, the accumulation by a subset of colon tumors of hundreds of thousands of somatic mutations in simple repeated sequences or microsatellites. We deduced that this enormous agglomeration of clonal mutations was due to the previous occurrence of 'mutator mutations' in DNA replication or repair factors leading to a decreased fidelity of replication. These mutator mutations appeared to be the remote cause for the development of these MMP tumors, whose existence unmistakably validated the hypothesis of 'cancer as a mutator phenotype'. Since these original observations, rapid progress has occurred in the field. The mutator mutations were identified as those occurring in members of the DNA mismatch repair gene family, which are also associated with hereditary non-polyposis colorectal cancer (HN-PCC). In this review I discuss the experimental approach th...Continue Reading

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.