Key Points
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Alterations in gene sequences, expression levels, and protein structure or function can be used as 'molecular markers' to detect cancers at an early stage, determine prognosis, and monitor disease progression or therapeutic response.
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DNA-based markers of cancer include mutations, loss-of-heterozygosity, microsatellite instability, DNA hypermethylation, mitochondrial DNA mutations and detection of viral DNA.
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There are various ways of detecting cancer cells by analysing RNA.
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Techniques to identify alterations in protein structure or function that are associated with cancer include antibody-based detection methods, measurement of enzymatic activity and two-dimensional gel analysis of samples.
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New approaches to discovering molecular markers include microarray analysis, serial analysis of gene expression and proteomic technologies.
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Clinical researchers should design future trials to incorporate plans for collecting and analysing molecular markers. Molecular biologists should take advantage of the number of tumour samples now available in tissue banks to identify new molecular markers and to more fully assess existing ones.
Abstract
Alterations in gene sequences, expression levels and protein structure or function have been associated with every type of cancer. These 'molecular markers' can be useful in detecting cancer, determining prognosis and monitoring disease progression or therapeutic response. But what is the best way to identify molecular markers and can they be easily incorporated into the clinical setting?
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Acknowledgements
The author would like to thank S. M. Hanash and G. W. Hart for their critical review. Supported by a National Institute of Health grant, as part of the Early Detection Research Network.
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Glossary
- MICROSATELLITE DNA
-
Repetitive stretches of short DNA sequences.
- SINGLE-NUCLEOTIDE-POLYMORPHISM (SNP) ANALYSIS
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Analysis based on single base-pair changes in DNA that differ among individuals. SNPs can be identified by various molecular means.
- CpG ISLANDS
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A region of DNA with a high density of cytosine–phospho-guanine nucleotides, which are usually located in the promoter region or the first exons of a gene. CpG islands are involved in the regulation of transcription, because their methylation can lead to permanent silencing of the associated gene.
- BRONCHOALVEOLAR LAVAGE FLUID
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A fluid sample that is obtained by inserting a tube into the lung.
- NESTED PCR
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Amplification of a DNA sequence that entails one initial amplification with a set of primers, followed by a second amplification with a set of internal (nested) primers, to allow a more robust amplification.
- REAL-TIME PCR
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The ability to monitor the linear phase of PCR during the actual amplification stages, usually by means of a fluorogenic compound and a laser to detect the accumulation of amplification products.
- MITOCHONDRIAL D-LOOP
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A section of the mitochondrial genome that is thought to be involved in replication, and contains short poly-pyrimidine tracts.
- HOMOPLASMIC
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The presence of identical genomes within all of the mitochondrial organelles in a cell.
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Sidransky, D. Emerging molecular markers of cancer. Nat Rev Cancer 2, 210–219 (2002). https://doi.org/10.1038/nrc755
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DOI: https://doi.org/10.1038/nrc755
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