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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References
Demicheli, R., Abbattista, A., Miceli, R., Valagussa, P. & Bonadonna, G. Time distribution of the recurrence risk for breast cancer patients undergoing mastectomy: further support about the concept of tumor dormancy. Breast Cancer Res. Treat. 41, 177–185 (1996).
Weigelt, B., Peterse, J. L. & van't Veer, L. J. Breast cancer metastasis: markers and models. Nature Rev. Cancer 5, 591–602 (2005).
van't Veer, L. J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530–536 (2002).
Ye, Q. H. et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nature Med. 9, 416–423 (2003).
Roepman, P. et al. An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nature Genet. 37, 182–186 (2005).
Huang, E. et al. Gene expression predictors of breast cancer outcomes. Lancet 361, 1590–1596 (2003).
Cromer, A. et al. Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis. Oncogene 23, 2484–2498 (2004).
Ramaswamy, S., Ross, K. N., Lander, E. S. & Golub, T. R. A molecular signature of metastasis in primary solid tumors. Nature Genet. 33, 49–54 (2003).
Bernards, R. & Weinberg, R. A. A progression puzzle. Nature 418, 823 (2002).
Weigelt, B. et al. Gene expression profiles of primary breast tumors maintained in distant metastases. Proc. Natl Acad. Sci. USA 100, 15901–15905 (2003).
Fidler, I. J. & Kripke, M. L. Genomic analysis of primary tumors does not address the prevalence of metastatic cells in the population. Nature Genet. 34, 23 (2003).
Schadt, E. E. et al. Genetics of gene expression surveyed in maize, mouse and man. Nature 422, 297–302 (2003).
Chesler, E. J. et al. Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nature Genet. 37, 233–242 (2005).
Bystrykh, L. et al. Uncovering regulatory pathways that affect hematopoietic stem cell function using “genetical genomics”. Nature Genet. 37, 225–232 (2005).
Eppig, J. T. et al. The Mouse Genome Database (MGD): from genes to mice — a community resource for mouse biology. Nucleic Acids Res. 33, D471–D475 (2005).
Gould, K. A. et al. Genetic evaluation of candidate genes for the Mom1 modifier of intestinal neoplasia in mice. Genetics 144, 1777–1785 (1996).
Dragani, T. A. et al. Mapping of melanoma modifier loci in RET transgenic mice. Jpn. J. Cancer Res. 91, 1142–1427 (2000).
Samuelson, D. J. et al. Physical evidence of Mcs5, a QTL controlling mammary carcinoma susceptibility, in congenic rats. Carcinogenesis 24, 1455–1460 (2003).
Reilly, K. M. et al. Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. Proc. Natl Acad. Sci. USA 101, 13008–13013 (2004).
Lifsted, T. et al. Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression. Int. J. Cancer 77, 640–644 (1998).
Hunter, K. W. et al. Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. Cancer Res. 61, 8866–8872 (2001).
Park, Y. G. et al. Sipa1 is a candidate for the metastasis efficiency modifier locus Mtes1. Nature Genet. 10, 1055–1062 (2005).
Qiu, T. H. et al. Global expression profiling identifies signatures of tumor virulence in MMTV-PyMT-transgenic mice: correlation to human disease. Cancer Res. 64, 5973–5981 (2004).
Hunter, K. W., Welch, D. R. & Liu, E. T. Genetic background is an important determinant of metastatic potential. Nat. Genet. 34, 23–24 (2003).
Talmadge, J. E., Wolman, S. R. & Fidler, I. J. Evidence for the clonal origin of spontaneous metastases. Science 217, 361–363 (1982).
Cheung, S. T. et al. Identify metastasis-associated genes in hepatocellular carcinoma through clonality delineation for multinodular tumor. Cancer Res. 62, 4711–4721 (2002).
Malins, D. C. et al. Metastatic cancer DNA phenotype identified in normal tissues surrounding metastasizing prostate carcinomas. Proc. Natl Acad. Sci. USA 101, 11428–11431 (2004).
Li, R., Lyons, M. A., Wittenburg, H., Paigen, B. & Churchill, G. A. Combining data from multiple inbred line crosses improves the power and resolution of quantitative trait loci mapping. Genetics 169, 1699–1709 (2005).
Ein-Dor, L., Kela, I., Getz, G., Givol, D. & Domany, E. Outcome signature genes in breast cancer: is there a unique set? Bioinformatics 21, 171–178 (2005).
Yang, H. et al. Caffeine suppresses metastasis in a transgenic mouse model: a prototype molecule for prophylaxis of metastasis. Clin. Exp. Metastasis 21, 719–735 (2005).
Ruggiero, M. et al. Vitamin D receptor gene polymorphism is associated with metastatic breast cancer. Oncol. Res. 10, 43–46 (1998).
Larkin, J. E., Frank, B. C., Gavras, H., Sultana, R. & Quackenbush, J. Independence and reproducibility across microarray platforms. Nature Methods 2, 337–344 (2005).
Irizarry, R. A. et al. Multiple-laboratory comparison of microarray platforms. Nature Methods 2, 345–350 (2005).
Bammler, T. et al. Standardizing global gene expression analysis between laboratories and across platforms. Nature Methods 2, 351–356 (2005).
Conrads, T. P., Zhou, M., Petricoin, E. F. 3rd, Liotta, L. & Veenstra, T. D. Cancer diagnosis using proteomic patterns. Expert Rev. Mol. Diagn. 3, 411–420 (2003).
Ben-Eliyahu, S. The promotion of tumor metastasis by surgery and stress: immunological basis and implications for psychoneuroimmunology. Brain Behav. Immun. 17 (Suppl.), S27–S36 (2003).
Harris, M., Winship, I. & Spriggs, M. Controversies and ethical issues in cancer-genetics clinics. Lancet Oncol. 6, 301–310 (2005).
Rabino, I. Genetic testing and its implications: human genetics researchers grapple with ethical issues. Sci. Technol. Human Values 28, 365–402 (2003).
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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Glossary
- Quantitative trait locus
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A quantitative trait locus (QTL) is a genetic locus that has a quantitative effect on the expression of a given phenotype.
- eQTL
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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
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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
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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
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Progeny resulting from the outcross between two genetically distinct individuals.
- F2 intercross
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Progeny resulting from the intercross of two F1 hybrid individuals, used for genetic mapping experiments.
- Recombinant, inbred mapping panel
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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
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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
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A hybridization method to detect and measure relative amplifications or deletions in cells.
- Fourier transform infrared microscopic spectrophotometry
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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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DOI: https://doi.org/10.1038/nrc1803
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