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Host genetics influence tumour metastasis

Abstract

The complexity of the metastatic process has made it difficult to gain a full understanding of the origins of this most lethal aspect of cancer. Many factors probably have an important role, including somatic mutation, epigenetic modulations, interactions with normal stroma, and environmental stimuli. Additionally, recent evidence implies a significant role for germline polymorphisms in cancer progression. The existence of inherited metastasis risk factors (or prospective metastatic biomarkers) has potentially significant implications for our models of metastasis, clinical prognosis and the development of tailored treatment. Further investigations into the inherited components of metastasis might help resolve many of the questions that remain about tumour progression.

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Figure 1: Models of the origins of metastases.
Figure 2: The effect of maternal genotype on the metastatic capacity of a polyoma middle-T antigen-expressing tumour.
Figure 3: A model of the influence of genetic background on metastatic efficiency.
Figure 4: Comparing the different factors that might influence tumour-gene- and metastasis-gene-expression patterns.

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Acknowledgements

I would like to thank Lalage Wakefield and Glenn Merlino for critical reading of this manuscript. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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DATABASES

National Cancer Institute

brain tumour

breast cancer

colon tumour

hepatocellular carcinoma

melanoma

Glossary

Quantitative trait locus

A quantitative trait locus (QTL) is a genetic locus that has a quantitative effect on the expression of a given phenotype.

eQTL

A quantitative trait locus (QTL) that has a quantitative effect on the level of expression of a given mRNA. Usually detected by performing gene-expression microarray analysis on a genetic mapping cross.

cis-eQTLs

A quantitative trait locus (QTL) that effects the expression of a given mRNA that lies nearby on the same chromosome as the gene in question. These are usually thought to be promoter or enhancer polymorphisms.

trans-eQTLs

A quantitative trait locus (QTL) that effects the expression of a given mRNA that either lies on the same chromosome but at a significant distance from the gene in question, or resides on a different chromosome. These are thought to be polymorphisms in transcription factors or genes that are upstream in the transcriptional cascade for the target mRNA.

F1 hybrid

Progeny resulting from the outcross between two genetically distinct individuals.

F2 intercross

Progeny resulting from the intercross of two F1 hybrid individuals, used for genetic mapping experiments.

Recombinant, inbred mapping panel

A specialized genetic-mapping tool that is based on a series of inbred animals that contain an approximately equal mixture of the genomes from two progenitor strains. These are produced by inbreeding F2 individuals.

Metastasis-suppressor gene

A gene that, when introduced into a metastatic cell line, suppresses the ability of the cell line to successfully metastasize but has minimal or no effect on primary tumour initiation or growth.

Comparative genome hybridization

A hybridization method to detect and measure relative amplifications or deletions in cells.

Fourier transform infrared microscopic spectrophotometry

Infrared spectroscopy method in which the absorption, reflection, emission or photoacoustic spectrum is obtained by Fourier transform (a mathematical technique for converting time-domain data to frequency-domain data) of an optical interference pattern.

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Hunter, K. Host genetics influence tumour metastasis. Nat Rev Cancer 6, 141–146 (2006). https://doi.org/10.1038/nrc1803

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