Abstract
In this chapter we describe an approach to the analysis of human tumors that emphasizes the performance of multiple simultaneous measurements on each of several thousand cells in each tumor sample. This approach can be implemented using such technologies as flow cytometry, laser-scanning cytometry, or high-resolution image analysis. Here we will focus on flow cytometry studies. Before proceeding to methodological details, we would like to consider the theoretical and practical advantages of performing cell-based measurements (vis a vis gel or array based measurements, for example), and in particular, the advantages of performing multiple measurements per cell.
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References
Pauletti, G., Dandekar, S., Rong, H., Ramos, L., Peng, H., Seshadri, R., and Slamon, D. (2000) Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J. Clin. Oncol. 18, 3651ā3664.
Slamon, D., Clark, G., Wong, S., Levin, W., Ullrich, A., and McGuire, W. (1987) Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177ā182.
Tsuda, H., Fukutomi, T., and Hirohashi, S. (1995) Pattern of gene alterations in intraductal breast neoplasms associated with histological type and grade. Clin. Cancer Res. 1, 261ā267.
Courjal, F., Cuny, M., Simony-Lafontaine, J., Louason, G., Speiser, P., Zeillinger, R., et al. (1997) Mapping of DNA amplifications at 15 chromosomal localizations in 1875 breast tumors: definition of phenotypic groups. Cancer Res. 57, 4360ā4367.
Shackney, S. and Shankey, T. (1997) Common patterns of genetic evolution in human solid tumors. Cytometry 29, 1ā27.
Hovey, R., Chu, L., Balasz, M., DeVries, S., Moore, D., Sauter, G., et al. (1998) Genetic alterations in primary bladder cancers and their metastases. Cancer Res. 58, 3555ā3560.
Lengauer, C., Kinzler, K., and Vogelstein, B. (1997) Genetic instability in colorectal cancers. Nature 386, 623ā627.
Janocko, L., Brown, K., Smith, C., Gu, L., Pollice, A., Singh, S., et al. (2001) Distinctive patterns of Her-2/neu, c-myc, and cyclin D1 gene amplification by fluorescence in situ hybridization (FISH) in primary human breast cancers. Cytometry (Communications in Clinical Cytometry) 148, 136ā149.
Shackney, S., Pollice, A., Smith, C., Alston, L., Singh, S., Janocko, L., et al. (1996) The accumulation of multiple genetic abnormalities in individual tumor cells in human breast cancers: Clinical prognostic implications. Cancer J. 2, 106ā113.
Shackney, S., Pollice, A., Smith, C., Janocko, L., Sweeney, L., Brown, K., et al. (1998) Intracellular coexpression of epidermal growth factor receptor, Her-2/neu, and p21ras in human breast cancers: evidence for the existence of distinctive patterns of genetic evolution that are common to tumors from different patients. Clin. Cancer Res. 4, 913ā928.
Smith, C., Pollice, A., Gu, L.-P., Brown, K., Singh, S., Janocko, L., et al. (2000) Correlations among p53, Her-2/neu, and ras overexpression and aneuploidy by multiparameter flow cytometry in human breast cancer: evidence for a common phenotypic evolutionary pattern in infiltrating ductal carcinomas. Clin. Cancer Res. 6, 112ā126.
Fearon, E. and Vogelstein, A. (1990) A genetic model for colorectal tumorigenesis. Cell 61, 759ā767.
Ried, T., Heselmeyer-Haddad, K., Blegen, H., Schrock, E., and Auer, G. (1999) Genomic changes defining the genesis, progression, and malignancy potential in solid human tumors: a phenotype/genotype correlation. Genes Chromosomes Cancer 25, 195ā204.
Galipeau, P., Cowan, D., Sanchez, C., Barrett, M., Emond, M., Levine, D., et al. (1996) 17P (p53) allelic losses, 4N (G2/tetraploid) populations and progression to aneuploidy in Barrettās esophagus. Proc. Natl. Acad. Sci. USA, 93, 7081ā7084.
Blount, P., Galipeau, P., Sanchez, C., Neshat, K., Levine, D., Yin, J., et al. (1994) 17p allelic losses in diploid cells of patients with Barrettās esophagus who develop aneuploidy. Cancer Res. 54, 2292ā2295.
Barrett, M., Sanchez, C., Prevo, L., Wong, D., Galipeau, P., Paulson, T., et al. (1999) Evolution of neoplastic cell lineages in Barrett Oesophagus. Nature Genet. 22, 106ā109.
Carder, P., Wyllie, A., Purdie, C., Morris, R., White, S., Piris, J., and Bird, C. (1993) Stabilized p53 facilitates aneuploid clonal divergence in colorectal cancer. Oncogene 8, 1397ā1401.
Carder, P., Cripps, K., Morris, R., Collins, S., White, S., Bird, C., and Wyllie, A. (1995) Mutation of the p53 gene precedes aneuploid clonal divergence in colorectal carcinoma. Br. J. Cancer 71, 215ā218.
Wistuba, I., Behrens, C., Milchgrub, S., Bryant, D., Hung, J., Minna, J., and Gazdar, A. (1999) Sequential molecular abnormalities are involved in the multistage development of squamous cell lung carcinoma. Oncogene 18, 643ā650.
Hung, J., Kishimoto, Y., Sugio, K., Virmani, A., McIntire, D., Minna, J., and Gazdar, A. (1995) Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA 273, 558ā563.
Kishimoto, Y., Sugio, K., Hunbg, J., Virmani, A., McIntire, D., Minna, J., and Gazdar, A. (1995) allele-specific loss in chromosone 9p loci in preneoplastic lesions accompanying non-small-cell lung Cancers. J. Nat. Cancer Insti. 87, 1224ā1229.
Belinsky, S., Nikula, K., Palmisano, W., Michels, R., Saccomano, G., Gabrielson, E., et al. (1998) Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis. Proc. Natl. Acad. Sci. USA 95, 11891ā11896.
Chung, G., Sundaresan, V., Hasleton, P., Rudd, R., Taylor, R., and Rabbitts, P. (1995) Sequential molecular genetic changes in lung cancer development. Oncogene 11, 2591ā2598.
Shackney, S., Smith, C., Pollice, A., Levitt, M., Magovern, J., Wiechmann, R., et al. (1999) Genetic evolutionary staging of early non-small cell lung cancer: the p53āHER-2/NEUāRas sequence. J. Thorac. Cardiovasc. Surg. 118, 259ā269.
Livingstone, L., White, A., Sprouse, J., Livanos, E., Jacks, T., and Tlsty, T. (1992) Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell 70, 923ā935.
Theillet, C., Lidereau, R., Escot, C., Hutzell, P., Brunet, M., Gest, J., et al. (1986) Loss of a c-H-ras-1 allele and aggressive human primary breast carcinomas. Cancer Res. 46, 4776ā4781.
Rochlitz, C., Scott, G., Dodson, J., Liu, E., Dollbaum, C., Smith, H., and Benz, C. (1989) Incidence of activating ras oncogene mutations associated with primary and metastatic human breast cancer. Cancer Res. 49, 357ā360.
Pollice, A., McCoy, J., J. P., Shackney, S., Smith, C., Agarwal, J., Burholt, D., et al. (1992) Sequential paraformaldehyde and methanol fixation for simultaneous flow cytometric analysis of DNA, cell surface proteins, and intracellular proteins. Cytometry 13, 432ā444.
Shackney, S., Berg G., Simon S., Cohen J., Amina S., Pommersheim W., et al. (1995) Origins and clinical implications of aneuploidy in early bladder cancer. Cytometry 22, 307ā316.
Shackney, S., Singh, S., Yakulis, R., Smith, C., Pollice, A., Petruolo, S., Waggoner, A., and Hartsock, R. (1995) Aneuploidy in breast cancer: a fluorescence in situ hybridization study. Cytometry 22, 282ā291.
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Shackney, S.E., Smith, C.A., Pollice, A.A., Silverman, J.F. (2003). Reconstruction of Geno-Phenotypic Evolutionary Sequences from Intracellular Patterns of Molecular Abnormalities in Human Solid Tumors. In: Driscoll, B. (eds) Lung Cancer. Methods in Molecular Medicineā¢, vol 75. Humana Press, Totowa, NJ. https://doi.org/10.1385/1-59259-324-0:431
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DOI: https://doi.org/10.1385/1-59259-324-0:431
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