Lecture 8 ã Gene amplification and tumorigenesis: diagnostics and prognostics

Conjoint 538, Winter 2004

Reading

Correlation of array-based gene expression results and tumor prognosis:

Sorlie, T., Perou, C. M., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., et al. (2001). Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98, 10869-10874.

Overexpression observed by arrays and confirmed by CGH:

Pollack, J. R., Sorlie, T., Perou, C. M., Rees, C. A., Jeffrey, S. S., Lonning, P. E., Tibshirani, R., Botstein, D., Borresen-Dale, A. L., and Brown, P. O. (2002). Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc Natl Acad Sci U S A 99, 12963-12968.

Yeast as a model for tumorigenesis: specific translocations and amplification in yeast "evolved" by continuous growth in culture:

Dunham, M. J., Badrane, H., Ferea, T., Adams, J., Brown, P. O., Rosenzweig, F., and Botstein, D. (2002). Characteristic genome rearrangements in experimental evolution of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 99, 16144-16149.

Mechanism of gene amplification ã This paper is highly recommended paper reading, and though it won't be covered in lecture you will hear more about it at Minisymp 4:

Zhu, C., Mills, K. D., Ferguson, D. O., Lee, C., Manis, J., Fleming, J., Gao, Y., Morton, C. C., and Alt, F. W. (2002). Unrepaired DNA breaks in p53-deficient cells lead to oncogenic gene amplification subsequent to translocations. Cell 109, 811-821.

Historical interest, and good background ã One of the first array-based analyses of gene expression in individual tumor samples

Perou, C. M., Sorlie, T., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., Rees, C. A., Pollack, J. R., Ross, D. T., Johnsen, H., Akslen, L. A., et al. (2000). Molecular portraits of human breast tumours. Nature 406, 747-752.

An example of how global expression and genomic analysis can be used in diagnosis and treatment of a rare tumor:

Linn, S. C., et al. (2003). Gene expression patterns and gene copy number changes in dermatofibrosarcoma protuberans. Am J Pathol 163, 2383-2395.