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Molecular Mutations in Human Neoplastic Disease

Application of Nucleic Acid Technology in Assessment of Familial Risk, Diagnosis, and Prognosis of Human Cancers

  • Chapter
Molecular Diagnostics

Part of the book series: Pathology and Laboratory Medicine ((PLM))

  • 260 Accesses

Abstract

Cancer represents a significant health problem worldwide. The successful curative treatment of almost every form of this disease depends on early diagnosis, and in the case of solid tumors, surgical resection with or without adjuvant therapy. Intensive research efforts during the last two decades have increased our understanding of carcinogenesis and have identified a genetic basis for the multistep nature of cancer development (1–3). In several human tumor systems, specific genetic alterations have been shown to correlate with well defined histopathologic stages of tumor development and progression (4,5). Although the significance of molecular mutations to the etiological mechanisms of tumor development has been debated, a causal role for such genetic lesions is now commonly accepted for a number of human tumors. Thus, genetic lesions represent an integral part of the processes of neoplastic transformation and tumor progression, and as such represent potentially valuable markers for cancer detection and staging (6–9). Through the application of specific and sensitive nucleic acid methodologies, the clinical laboratory of the future will be able to effectively screen populations at high risk for the development of cancer, potentially impacting the early detection and diagnosis of human cancers. In addition, development of new molecular diagnostic assays will expand the ability of clinicians to accurately stage tumor development, monitor progression of metastatic disease, and evaluate therapeutic out-come, facilitating the application of effective intervention strategies in the treatment of human tumors.

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References

  1. Foulds, L. The natural history of cancer. J. Chronic Dis. 8:2–37, 1958

    Article  PubMed  CAS  Google Scholar 

  2. Weinberg, R. A. Oncogenes, antioncogenes, and the molecular bases of multistep carcinogenesis. Cancer Res. 49:3713–3721, 1989.

    PubMed  CAS  Google Scholar 

  3. Bishop, J. M. Molecular themes in oncogenesis. Cell 64:235–248, 1991.

    Article  PubMed  CAS  Google Scholar 

  4. Fearon, E. R. and Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61:757–767, 1990.

    Article  Google Scholar 

  5. Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Leppert, M., Nakamura, Y., White, R., Smits, M. M., and Bos, J. L. Genetic alterations during colorectal tumor devel-opment. New Engl. J. Med. 319:525–532, 1988.

    Article  PubMed  CAS  Google Scholar 

  6. Sidransky, D., Boyle, J., Koch, W., and van der Riet, P. Oncogene mutations as interme-diate markers. J. Cell. Biochem. Suppl. 17F:184–187, 1993.

    Article  Google Scholar 

  7. Sidransky, D. Molecular screening-How long can we afford to wait? J. Natl. Cancer Inst. 86:955–956, 1994.

    Article  PubMed  CAS  Google Scholar 

  8. Mao, L. and Sidransky, D. Cancer screening based on genetic alterations in human tumors. Cancer Res. 54:1939S–1940S, 1994.

    Google Scholar 

  9. Sidransky, D. Molecular markers in cancer: can we make better predictions? Int. J. Can-cer 64:1–2, 1995.

    Article  CAS  Google Scholar 

  10. Nowell, P. The clonal evolution of tumor cell populations. Science 194:23–38, 1976.

    Article  PubMed  CAS  Google Scholar 

  11. Renan, M. J. How many mutations are required for tumorigenesis? Implications from human cancer data. Mol. Carcinog. 7:139–146, 1993.

    Article  PubMed  CAS  Google Scholar 

  12. Sugarbaker, J. P., Gunderson, L. L., and Wittes, R. E. Colorectal cancer, in Cancer: Prin-ciples and Practice of Oncology, De Vita, V. T., Hellman, S., and Rosenberg, S. A., eds., Lippincott, Philadelphia, pp. 800–815, 1985.

    Google Scholar 

  13. Anderson, M. W., Reynolds, S. H., You, M., and Maronpot, R. M. Role of proto-oncogene activation in carcinogenesis. Environ. Health Perspect. 98:13–24, 1992.

    Article  PubMed  CAS  Google Scholar 

  14. Cooper, G. M. Oncogenes, 2nd ed., Jones and Bartlett Publishers, Boston, 1995.

    Google Scholar 

  15. Marshall, C. J. Tumor suppressor genes. Cell 64:313–326, 1991.

    Article  PubMed  CAS  Google Scholar 

  16. Friend, S. p53: a glimpse at the puppet behind the shadow play. Science 265:334–335, 1994.

    Article  PubMed  CAS  Google Scholar 

  17. Zambetti, G. P. and Levine, A. J. A comparison of the biological activities of wild-type and mutant p53. FASEB J. 7:855–865, 1993.

    PubMed  CAS  Google Scholar 

  18. Hollingsworth, R. E., Hensely, C. E., and Lee, W. H. Retinoblastoma protein and the cell cycle. Curr. Opinion Genet. Dev. 3:55–62, 1993.

    Article  CAS  Google Scholar 

  19. Perry, M. E. and Levine, A. J. Tumor-suppressor p53 and the cell cycle. Curr. Opinion Genet. Dev. 3:50–54, 1993.

    Article  CAS  Google Scholar 

  20. Bos, J. L. ras Oncogenes in human cancer: a review. Cancer Res. 49:4682–4689, 1989.

    PubMed  CAS  Google Scholar 

  21. Hollstein, M., Sidransky, D., Vogelstein, B., and Harris, C. C. p53 mutations in human cancers. Science 253:49–53, 1991.

    Article  PubMed  CAS  Google Scholar 

  22. Greenblatt, M. S., Bennett, W. P., Hollstein, M., and Harris, C. C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 54:4855.–4878, 1994.

    Google Scholar 

  23. Spitz, M. R. and Bondy, M. L. Genetic susceptibility to cancer. Cancer 72:991–995, 1993.

    Article  PubMed  CAS  Google Scholar 

  24. Friedberg, E. C. DNA Repair. Freeman, New York, 1985.

    Google Scholar 

  25. Coleman, W. B. and Tsongalis, G. J. Multiple mechanisms account for genomic instabil-ity and molecular mutation in neoplastic transformation. Clin. Chem. 41:644–657, 1995.

    PubMed  CAS  Google Scholar 

  26. Pines, J. Cyclins and their associated cyclin-dependent kinases in the human cell cycle. Biochem. Soc. Trans. 21:921–925, 1993.

    PubMed  CAS  Google Scholar 

  27. Cordon-Cardo, C. Mutation of cell cycle regulators. Biological and clinical implications for human neoplasia. Am. J. Pathol. 147:454–560, 1995.

    Google Scholar 

  28. Kinzler, K. W. and Vogelstein, B. The colorectal cancer gene hunt: current findings. Hosp. Pract. 27:37–44, 1992.

    Google Scholar 

  29. Bos, J. L., Fearon, E. R., Hamilton, S. R., Verlaan-de Vries, M., van Boom, J. H., van der Eb, A. J., and Vogelstein, B. Prevalence of ras gene mutations in human colorectal can-cers. Nature 327:293–297, 1987.

    Article  PubMed  CAS  Google Scholar 

  30. Baker, S. J., Fearon, E. R., Nigro, J. M., Hamilton, S. R., Preisinger, A. C., Jessup, J. M., van Tuinen, P., Ledbetter, D. H., Barker, D. F., Nakamura, Y., White, R., and Vogelstein, B. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221, 1989.

    Article  PubMed  CAS  Google Scholar 

  31. Feinberg, A. P., Gehrke, C. W., Kuo, K. C., and Ehrlich, M. Reduced genomic 5-methyl-cytosine content in human colonic neoplasia. Cancer Res. 48:1159–1161, 1988.

    PubMed  CAS  Google Scholar 

  32. Lee, W.-H, Bookstein, R., Hong, F., Young, L.-H., Shew, J.-Y., and Lee, E. Y.-H. P. Human retinoblastoma susceptability gene: cloning, identification, and sequence. Sci-ence 235:1394–1399, 1987.

    CAS  Google Scholar 

  33. Knudson, A. G. Mutation and cancer: a statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 68:820–823, 1971.

    Article  PubMed  Google Scholar 

  34. Li, F. P and Fraumeni, J. F., Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann. Intern. Med. 71:747–752, 1969.

    PubMed  CAS  Google Scholar 

  35. Li, F. P, Fraumeni, J. F., Jr., Mulvihill, J. J., Blattner, W. A., Dreyfus, M. G., Tucker, M. A., and Miller, R. W. A cancer family syndrome in 24 kindreds. Cancer Res. 48:5358–5362, 1988.

    PubMed  CAS  Google Scholar 

  36. Li, F. P and Fraumeni, J. F., Jr. Prospective study of a family cancer syndrome. JAMA 247:2692–2694, 1982.

    Article  PubMed  CAS  Google Scholar 

  37. Lustbader, E. D., Williams, W. R., Bondy, M. L., Strom, S., and Strong, L. C. Segrega-tion analysis of cancer families of childhood soft-tissue-sarcoma patients. Am. J. Hum. Genet. 51:344–356, 1992.

    PubMed  CAS  Google Scholar 

  38. Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Nelson, C. E., Kim, D. M., Kessel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., and Friend, S. Germ line mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:1233–1238, 1990.

    Article  PubMed  CAS  Google Scholar 

  39. Srivastava, S., Zou, Z., Pirollo, K., Blattner, W., and Chang, E. H. Germ-line transmis-sion of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348:747–749, 1990.

    Article  PubMed  CAS  Google Scholar 

  40. Birch, J. M., Hartley, A. L., Tricker, K. J., Prosser, J., Condie, A., Kelsey, A. M., Harris, M., Jones, P. H. M., Binchy, A., Crowther, D., Craft, A. W., Eden, O. B., Evans, D. G. R., Thompson, E., Mann, J. R., Martin, J., Mitchell, E. L. D., and Santibanez-Koref, M. F. Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. Cancer Res. 54:1298–1304, 1994.

    PubMed  CAS  Google Scholar 

  41. Birch, J. M. Familial cancer syndromes and clusters. Br. Med. Bull. 50:624 639, 1994.

    Google Scholar 

  42. Momand, J., Zambetti, G. P., Olson, D. C., George, D., and Levine, A. J. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237–1245, 1992.

    Article  PubMed  CAS  Google Scholar 

  43. Lynch, H. T., Lanspa, S., Smyrk, T., Boman, B., Watson, P., and Lynch, J. Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). Genetics, pathology, natural history, and cancer control, part I. Cancer Genet. Cytogenetics 53:143–160, 1991.

    Article  CAS  Google Scholar 

  44. Nishisho, I., Nakamura, Y., Miyoshi, Y., Miki, Y., Ando, H., Horii, A., Koyama, K., Utsunomiya, J., Baba, S., Hedge, P., Markham, A., Krush, A. J., Peterson, G., Hamilton, S. R., Nilbert, M. C., Levy, D. B., Bryan, T. M., Preisinger, A. C., Smith, K. J., Su, L., Kinzler, K. W., and Vogelstein, B. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253:665–669, 1991.

    Article  PubMed  CAS  Google Scholar 

  45. Groden, J., Thliveris, A., Samowitz, W., Carlson, M., Gelbert, L., Albertson, H., Joslyn, G., Stevens, J., Spiro, L., Robertson, M., Sargent, L., Krapcho, K., Wolff, E., Burt, R., Hughes, J. P., Warrington, J., McPherson, J., Wasmuth, J., Le Paslier, D., Abderrahim, H., Cohen, D., Leppert, M., and White, R. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589–600, 1991.

    Article  PubMed  CAS  Google Scholar 

  46. Kinzler, K. W., Nilbert, M. C., Su, L. K., Vogelstein, B., Bryan, T. M., Levy, D. B., Smith, K. J., Preisinger, A. C., Hedge, P., McKechnie, D., Finniear, R., Markham, A., Groffe, J., Boguski, M. S., Altschul, S. F., Horii, A., Ando, H., Miyoshi, Y., Miki, Y., Nishisho, I., and Nakamura, Y. Identification of a chromosome 5q21 gene that is mutated in colorectal cancers. Science 251:1366–1370, 1991.

    Article  PubMed  CAS  Google Scholar 

  47. Nagase, H., Miyoshi, Y., Horii, A., Aoki, T., Ogawa, M., Utsunomiya, J., Baba, S., Sasuki, T., and Nakamura, Y. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Res. 52:4055–4057, 1992.

    PubMed  CAS  Google Scholar 

  48. Su, L., Johnson, K. A., Smith, K. J., Hill, D. E., Vogelstein, B., and Kinzler, K. W. Asso-ciation between wild type and mutant APC gene products. Cancer Res. 53:2728–2731, 1993.

    PubMed  CAS  Google Scholar 

  49. Vasen, H. F. A., Offerhaus, G. J. A., den Hartog Jager, F. C. A., Menko, F. H., Nagengast, F. M., Griffioen, G., van Hogezand, R. B., and Heintz, A. P. M. The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in the Netherlands. Int. J. Cancer 46:31–34, 1990.

    Article  PubMed  CAS  Google Scholar 

  50. Mecklin, J.-P. and Jarvinen, H. J. Tumor spectrum in cancer family syndrome (hereditary nonpolyposis colorectal cancer). Cancer 68:1109–1112, 1991.

    Article  PubMed  CAS  Google Scholar 

  51. Peltomaki, P., Aaltonen, L. A., Sistonen, P., Pykkanen, L., Mecklin, J. P., Jarvinen, H., Green, J. S., Jass, J. R., Weber, J. L., Leach, F. S., Petersen, G. M., Hamilton, S. R., de la Chapelle, A., and Vogelstein, B. Genetic mapping of a locus predisposing to human colorectal cancer. Science 260:810–812, 1993.

    Article  PubMed  CAS  Google Scholar 

  52. Aaltonen, L. A., Peltomaki, P., Leach, F. S., Sistonen, P., Pylkkanen, L., Mecklin, J.-P., Jarvinen, H., Powell, S. M., Jen, J., Hamilton, S. R., Petersen, G. M., Kinzler, K. W., Vogelstein, B. and de la Chapelle, A. Clues to the pathogenesis of familial colorectal cancer. Science 260:812–816, 1993.

    Article  PubMed  CAS  Google Scholar 

  53. Thibodeau, S. N., Bren, G., and Schaid, D. Microsatellite instability in cancer of the proximal colon. Science 260:816–819, 1993.

    Article  PubMed  CAS  Google Scholar 

  54. Ionov, Y., Peinado, M. A., Malkhosyan, S., Shibata, D. and Perucho, M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363:558–561, 1993.

    Article  PubMed  CAS  Google Scholar 

  55. Aaltonen, L. A., Peltomaki, P., Mecklin, J.-P., Jarvinen, H., Jass, J. R., Green, J. S., Lynch, H. T., Watson, P., Tallqvist, G., Juhola, M., Sistonen, P., Hamilton, S. R., Kinzler, K. W., Vogelstein, B. and de la Chapelle, A. Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res. 54:1645–1648, 1994.

    PubMed  CAS  Google Scholar 

  56. Fishel, R., Lescoe, M. K., Rao, M. R. S., Copeland, N. G., Jenkins, N. A., Garber, J., Kane, M. and Kolodner, R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:1027–1038, 1993.

    Article  PubMed  CAS  Google Scholar 

  57. Leach, F. S., Nicolaides, N. C., Papadopoulos, N., Liu, B., Jen, J., Sistonen, P., Aaltonen, L. A., Nystrom-Lahti, M., Guan, X.-Y., Zhang, J., Meltzer, P. S., Yu, J.-W., Kao, F.-T., Chen, D. J., Cerosaletti, K. M., Fournier, R. E. K., Todd, S., Lewis, T., Leach, R. J., Naylor, S. L., Weissenbach, J., Mecklin, J.-P., Jarvinen, H., Petersen, G. M., Hamilton, S. R., Green, J., Jass, J., Watson, P., Lynch, H. T., Trent, J. M., de la Chapelle, A., Kinzler, K. W., and Vogelstein, B. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225, 1993.

    Article  PubMed  CAS  Google Scholar 

  58. Bronner, C. E., Baker, S. M., Morrison, P. T., Warren, G., Smith, L. G., Lescoe, M. K., Kane, M., Earabino, C., Lipford, J., Lindbloom, A., Tannergard, P., Bollag, R. J., Godwin, A. R., Ward, D. C., Nordenskjold, M., Fishel, R., Kolodner, R., and Liskay, R. M. Muta-tion in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 368:258–261, 1994.

    Article  PubMed  CAS  Google Scholar 

  59. Nicolaides, N. C., Papadopoulos, N., Liu, B., Wel, Y.-F., Carter, K. C., Ruben, S. M., Rosen, C. A., Haseltine, W. A., Fleischmann, R. D., Fraser, C. M., Adams, M. D., Venter, J. C., Dunlop, M. G., Hamilton, S. R., Petersen, G. M., de la Chapelle, A., Vogelstein, B., and Kinzler, K. W. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature 371:75–80, 1994.

    Article  PubMed  CAS  Google Scholar 

  60. Papadopoulos, N., Nicolaides, N. C., Wei, Y.-F., Ruben, S. M., Carter, K. C., Rosen, C. A., Haseltine, W. A., Fleishmann, R. D., Fraser, C. M., Adams, M. D., Venter, J. C., Hamilton, S. R., Petersen, G. M., Watson, P., Lynch, H. T., Peltomaki, P., Mecklin, J.-P., de la Chapelle, A., Kinzler, K. W., and Vogelstein, B. Mutation of a mutL homolog in hereditary colon cancer. Science 263:1625–1629, 1994.

    Article  PubMed  CAS  Google Scholar 

  61. Shibata, D., Peinado, M. A., Ionov, Y., Malkhosyan, S., and Perucho, M. Genomic insta-bility in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nature Genet. 6:273–281, 1994.

    Article  PubMed  CAS  Google Scholar 

  62. Parsons, R., Li, G.-M., Longley, M. J., Fang, W.-H., Papadopoulos, N., Jen, J., de la Chapelle, A., Kinzler, K. W., Vogelstein, B., and Modrich, P. Hypermutability and mis-match repair deficiency in RER+ tumor cells. Cell 75:1227–1236, 1993.

    Article  PubMed  CAS  Google Scholar 

  63. Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P. A., Harshman, K., Tavtigian, S., Liu, Q., Cochran, C., Bennett, M., Ding, W., Bell, R., Rosenthal, J., Hussey, C., Tran, T., McClure, M., Frye, C., Hattier, T., Phelps, R., Haugen-Strano, A., Katcher, H., Yakumo, K., Golami, Z., Shaffer, D., Stone, S., Bayer, S., Wray, C., Bogden, R., Dayananth, P., Ward, J., Tonin, P., Narod, S,A., Bristow, P., Norris, P., Helvering, L., Morrison, P., Rosteck, P., Lai, M., Barrett, C., Lewis, C., Neuhausen, S., Cannon-Albright, L., Goldgar, D., Wiseman, R., Kamb, A., and Skolnick, M. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:67–71, 1994.

    Article  Google Scholar 

  64. Wooster, R., Bignell, G., Lancaster, J., Swift, S., Seal, S., Mangion, J., Collins, N., Gre-gory, S., Gumbs, C., Micklem, G., Barfoot, R., Hamoudi, R., Patel, S., Rice, C., Biggs, P., Hashim, Y., Smith, A., Connor, F., Arason, A., Gundmundsson, J., Ficenec, D., Kelsell, D., Ford, D., Tonin, P., Bishop, D. T., Spurr, N. K., Ponder, B. A. J., Eeles, R., Peto, J., Devilee, P., Cornelisse, C., Lynch, H., Narod, S., Lenoir, G., Egilsson, V., Barkadottir, R. B., Easton, D. F., Bentley, D. R., Futreal, P. A., Ashworth, A., and Stratton, M. R. Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792, 1995.

    Article  PubMed  CAS  Google Scholar 

  65. Sobol, H., Neuhausen, S. L., and Eisinger, F. Evidence for a third breast-cancer suscepti-bility gene. Lancet 344:1151,1152, 1994.

    Google Scholar 

  66. Easton, D. F., Ford, D., Bishop, D. T., and the Breast Cancer Linkage Consortium. Breast and ovarian cancer incidence in BRCAI-mutation carriers. Am. J. Hum. Genet. 56:265– 271, 1995.

    Google Scholar 

  67. Easton, D. F., Bishop, D. T., Ford, D., Cockford, G. P., and the Breast Cancer Linkage Consortium. Genetic linkage analysis in familial breast and ovarian cancer. Am. J. Hum. Genet. 52:718–722, 1993.

    Google Scholar 

  68. Shattuck-Eidens, D., McClure, M., Simard, J., Labrie, F., Narod, S., Couch, F., Hoskins, K., Weber, B., Castilla, L., Erdos, M., Brody, L., Friedman, L., Ostermeyer, E., Szabo, C., King, M.-C., Jhanwar, S., Offit, K., Norton, L., Gilewski, T., Lubin, M., Osborne, M., Black, D., Boyd, M., Steel, M., Ingles, S., Haile, R., Lindblom, A., Olsson, H., Borg, A., Bishop, D. T., Solomon, E., Radice, P., Spatti, G., Gayther, S., Ponder, B., Warren, W., Stratton, M., Liu, Q., Fujimura, F., Lewis, C., Skolnick, M. H., and Goldgar, D. E. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer suscepti-bility gene: implications for presymptomatic testing and screening. JAMA 273:535– 541, 1995.

    Google Scholar 

  69. Futreal, P. A., Liu, Q., Shattuck-Eidens, D., Cochran, C., Harshman, K., Tavtigian, S., Bennett, L. M., Haugen-Strano, A., Swensen, J., Miki, Y., Eddington, K., McClure, M., Frye, C., Weaver-Feidhaus, J., Ding, W., Gholami, Z., Soderkvist, P., Terry, L., Jhanwar, S., Berchuck, A., Inglehart, J. D., Marks, J., Ballinger, D. G., Barrett, J. C., Skolnick, M. H., Kamb, A., and Wiseman, R. BRCA1 mutations in primary breast and ovarian carci-nomas. Science 266:120–122, 1994.

    CAS  Google Scholar 

  70. Gayther, S. A., Warren, W., Mazoyer, S., Russell, P. A., Harrington, P. A., Chiano, M., Seal, S., Hamoudi, R., van Rensburg, E. J., Dunning, A. M., Love, R., Evans, G., Easton, D., Clayton, D., Stratton, M. R., and Ponder, B. A. J. Germline mutations of the BRCA 1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nature Genet. 11:428–433, 1995.

    Article  PubMed  CAS  Google Scholar 

  71. Wooster, R., Neuhausen, S., Mangion, J., Quirk, Y., Ford, D., Collins, N., Nguyen, K., Seal, S., Tran, T., Averill, D., Fields, P., Marshall, G., Narod, S., Lenoir, G., Lynch, H. T., Feunteun, J., Devilee, P., Cornelisse, C., Menko, F., Daley, P., Ormiston, W., McManus, R., Pye, C., Lewis, C., Cannon-Albright, L., Peto, J., Pon-der, B. A. J., Skolnick, M., Easton, D., Godgar, D., and Stratton, M. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265:2088–2090, 1994.

    Google Scholar 

  72. Albino, A. P. Genes involved in melanoma susceptibility and progression. Curr. Opinion Oncol. 7:162–169, 1995.

    Article  CAS  Google Scholar 

  73. Bale, S. J., Chakravarti, A., and Greene, M. H. Cutaneous malignant melanoma and familial dysplastic nevi: evidence for autosomal dominance and pleiotropy. Am. J. Hum. Genet. 38:188–196, 1986.

    PubMed  CAS  Google Scholar 

  74. Cannon-Albright, L., Goldgar, D., Meyer, L., Lewis, C., Anderson, D., Fountain, J., Hegi, M., Wiseman, R., Petty, E., and Bale, A. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13–p22. Science 258:1148–1152, 1992.

    Google Scholar 

  75. Goldstein, A., Dracopoli, N., Engelstein, M., Fraser, M., Clark, W. Jr., Tucker, M. Fur-ther evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/ DN) on chromosome lp, and evidence for genetic heterogeneity. Am. J. Hum. Genet. 52:537–550, 1993.

    PubMed  CAS  Google Scholar 

  76. Kamb, A., Gruis, N. A., Weaver-Feldhaus, J., Lui, Q., Harshman, K., Tavtigian, S. V., Stockert, E., Day, R. S., Johnson, B. E., and Skolnick, M. H. A cell cycle regu-lator potentially involved in genesis of many tumor types. Science 264:436–440, 1994.

    Article  PubMed  CAS  Google Scholar 

  77. Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K. and Carson, D. A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368:753–756, 1994.

    Article  PubMed  CAS  Google Scholar 

  78. Hussussian, C. J., Strvewing, J. P., Goldstein, A. M., Higgins, P. A. T., Ally, D. S., Sheahan, M. D., Clark, W. H., Jr., Tucker, M. A., and Dracopoli, N. C. Germline p16 mutations in familial melanoma. Nature Genet. 8:15–21, 1994.

    Article  PubMed  CAS  Google Scholar 

  79. Kamb, A., Shattuck-Eidens, D., Eeles, R., Liu, Q., Gruis, N. A., Ding, W., Hussey, C., Tran, T., Miki, Y., Weaver-Feldhaus, J., McClure, M., Aitken, J. F., Anderson, D. E., Bergman, W., Frants, R., Goldgar, D. E., Green, A., MacLennan, R., Martin, N. G., Meyer, L. J., Youl, P., Zone, J. J., Skolnick, M. H., and Cannon-Albright, L. A. Analysis of the p I 6 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nature Genet. 8:22–26, 1994.

    Article  CAS  Google Scholar 

  80. Ohta, M., Nagai, H., Shimizu, M., Rasio, D., Berd, D., Mastrangelo, M., Singh, A. D., Shields, J. A., Shields, C. A., Croce, C. M., and Heubner, K. Rarity of somatic and germline mutations of the cyclin dependent kinase 4 inhibitor gene, CDK4I, in mela-noma. Cancer Res. 54:5269–5272, 1994.

    PubMed  CAS  Google Scholar 

  81. Zuo, L., Weger, J., Yang, Q., Goldstein, A. M., Tucker, M. A., Walker, G. J., Hayward, N., and Dracopoli, N. C. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nature Genet. 12:97–99, 1996.

    Article  PubMed  CAS  Google Scholar 

  82. Cleaver, J. E. and Kraemer, K. H. Xeroderma pigmentosum and Cockayne sundrome, in The Metabolic and Molecular Bases of Inherited Disease, 7th ed., Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds., McGraw-Hill Inc., New York, pp. 4393–4419, 1995.

    Google Scholar 

  83. Boder, E. Ataxia-telangiectasia: an overview, in Ataxia-telangiectasia: Genetics, Neuropathology, and Immunology ofa Degenerative Disease of Childhood, Gatti, R. A. and Swift, M., eds., Liss, New York, pp. 1–63, 1985.

    Google Scholar 

  84. Swift, M., Morrell, D., Massey, R. B., and Chase, C. L. Incidence of cancer in 161 fami-lies affected by ataxia-telangiectasia. New Engl. J. Med. 325:1831–1836, 1991.

    Article  PubMed  CAS  Google Scholar 

  85. German, J. and Passarge, E. Bloom’s syndrome. XII. Report from the Registry for 1987. Clin. Genet. 35:57–69, 1989.

    Article  PubMed  CAS  Google Scholar 

  86. Gatti, R. A. Localizing the genes for ataxia telangiectasia: a human model for inherited cancer susceptibility. Adv. Cancer Res. 56:77–104, 1991.

    Article  PubMed  CAS  Google Scholar 

  87. Digweed, M. Human genetic instability syndromes: single gene defects with increased risk of cancer. Toxicol. Lett. 67:659–681, 1993.

    Article  Google Scholar 

  88. Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D. A., Smith, S., Uziel, T., Sfez, S., Ashkenazi, M., Pecker, I., Frydman, M., Harnik, R., Patanjali, S. R., Simmons, A., Clines, G. A., Sartiel, A., Gatti, R. A., Chessa, L., Sanal, O., Lavin, M. F., Jaspers, N. G. J., Taylor, A. M. R., Arlett, C. F., Miki, T., Weissman, S. M., Lovett, M., Collins, F. S., and Shiloh, Y. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749–1753, 1995.

    Article  PubMed  CAS  Google Scholar 

  89. Gutmann, D. H. and Collins, F. S. von Recklinghausen neurofibromatosis, in The Meta-bolic and Molecular Bases ofInherited Disease, 7th ed., Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds., McGraw-Hill, New York, pp. 677–696, 1995.

    Google Scholar 

  90. Carlson, K. M., Dou, S., Chi, D., Scavarda, N., Toshima, K., Jackson, C. E., Wells, S. A., Jr., Goodfellow, P. J., and Donis-Keller, H. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with mul-tiple endocrine neoplasia type 2B. Proc. Natl. Acad. Sci. USA 91:1579–1583, 1994.

    Article  PubMed  CAS  Google Scholar 

  91. Haber, D. A. and Housman, D. E. Wilms tumor, in The Metabolic and Molecular Bases of Inherited Disease, 7th ed., Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle. D., eds., New York: McGraw-Hill, pp. 665–676, 1995.

    Google Scholar 

  92. Levin, B. Colorectal cancer screening. Cancer 72:1056–1060, 1993.

    Article  PubMed  CAS  Google Scholar 

  93. Sidransky, D., Tokino, T., Hamilton, S. R., Kinzler, K. W., Levin, B., Brost, P., and Vogelstein, B. Identification of ras oncogene mutations in the stool of patients with cur-able colorectal tumor. Science 256:102–105, 1992.

    Article  PubMed  CAS  Google Scholar 

  94. Tobi, M., Luo, F.-C., and Ronai, Z. Detection of K-ras mutation in colonic effluent samples from patients without evidence of colorectal carcinoma. J. Natl. Cancer Inst. 86:1007–1010, 1994.

    Article  PubMed  CAS  Google Scholar 

  95. Powell, S. M., Petersen, G. M., Krush, A. J., Booker, S., Jen, J., Giardiello, F. M., Hamilton, S. R., Vogelstein, B., and Kinzler, K. W. Molecular diagnosis of familial adenomatous polyposis. New Engl. J. Med. 329:1982–1987, 1993.

    Article  PubMed  CAS  Google Scholar 

  96. Mao, L., Hruban, R. H., Boyle, J. O., Tockman, M. and Sidransky, D. Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer Res. 54:1634–1637, 1994.

    PubMed  CAS  Google Scholar 

  97. Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N., and Perucho, M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–554, 1988.

    Article  PubMed  CAS  Google Scholar 

  98. Urban, T., Ricci, S., Grange, J.-D., Lacave, R., Boudghene, F., Breittmayer, F., Languille, O., Roland, J., and Bernaudin, J.-F. Detection of c-Ki-ras mutation by PCR/RFLP analysis and diagnosis of pancreatic adenocarcinomas. J. Natl. Cancer Inst. 85:2008–2012, 1993.

    Article  PubMed  CAS  Google Scholar 

  99. Berthelemy, P., Bouisson, M., Escourrou, J., Vaysse, N., Rumeau, J. L., and Pradayrol, L. Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancre-atic cancer. Ann. Intern. Med. 123:188–191, 1995.

    PubMed  CAS  Google Scholar 

  100. Tada, M., Omata, M., Kawai, S., Saisho, H., Ohto, M., Saiki, R. K., and Sninsky, J. J. Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res. 53:2472–2474, 1993.

    PubMed  CAS  Google Scholar 

  101. Caldas, C., Hahn, S. A., Hruban, R. H., Redston, M. S., Yeo, C. J., and Kern, S. E. Detec-tion of K-ras mutations in stool of patients with pancreatic adenocarcinoma and pancre-atic ductal hyperplasia. Cancer Res. 54:3568–3573, 1994.

    PubMed  CAS  Google Scholar 

  102. Goh, H.-S., Yao, J., and Smith, D. R. p53 point mutation and survival in colorectal cancer patients. Cancer Res. 55:5217–5221, 1995.

    PubMed  CAS  Google Scholar 

  103. Hamelin, R., Laurent-Puig, P., Olschwang, S., Jego, N., Asselain, B., Remvikos, Y., Girodet, J., Salmon, R. J., and Thomas, G. Association of p53 mutations with short sur-vival in colorectal cancer. Gastroenterology 106:42–48, 1994.

    PubMed  CAS  Google Scholar 

  104. Jen, J., Kim, H., Piantadosi, S., Liu, Z.-F., Levitt, R. C., Sistonen, P., Kinzler, K. W., Vogelstein, B., and Hamilton, S. R. Allelic loss of chromosome 18q and prognosis in colorectal cancer. New Engl. J. Med. 331:213–221, 1994.

    Article  PubMed  CAS  Google Scholar 

  105. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgi-cally treated rectal carcinoma. New Engl. J. Med. 312:1465–1472, 1985.

    Article  Google Scholar 

  106. Saitoh, S., Cunningham, J., De Vries, E. M. G., McGovern, R. M., Schroeder, J. J., Hartmenn, A., Blaszyk, H, Wold, L. E., Schaid, D., Sommer, S. S., and Kovach, J. S. p53 gene mutations in breast cancers in midwestern US women: null as well as missense-type mutations are associated with poor prognosis. Oncogene 9:2869–2875, 1994.

    PubMed  CAS  Google Scholar 

  107. Thorlacius, S., Borresen, A.-L., and Eyfjord, J. E. Somatic p53 mutations in human breast carcinomas in an Icelandic population: a prognostic factor. Cancer Res. 53:1637–1641, 1993.

    PubMed  CAS  Google Scholar 

  108. Kovach, J. S., Hartmann, A., Blaszyk, H., Cunningham, J., Schaid, D., and Sommer, S. S. Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value. Proc. Natl. Acad. Sci. USA 93:1093–1096, 1996.

    Article  PubMed  CAS  Google Scholar 

  109. Henson, D. E., Fielding, L. P., Grignon, D. J., Page, D. L., Hammond, M. E., Nash, G., Pettigrew, N. M., Gorstein, F., and Hutter, R. V. P. College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors: summary. Arch. Pathol. Lab. Med. 119:1109–1112,1995.

    PubMed  CAS  Google Scholar 

  110. Fielding, L. P. and Pettigrew, N. College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors: report of the colorectal cancer working group. Arch. Pathol. Lab. Med. 119:1115–1121, 1995.

    PubMed  CAS  Google Scholar 

  111. Grignon, D. J. and Hammond E. H. College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumors: report of the prostate cancer working group. Arch. Pathol. Lab. Med. 119:1122–1126, 1995.

    PubMed  CAS  Google Scholar 

  112. Wright, P. A. and Wynford-Thomas, D. Mutations in familial cancer. J. Pathol. 172:167–170, 1994.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. William B. Coleman
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  2. Gregory J. Tsongalis
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Editors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    William B. Coleman

  2. Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT, USA

    Gregory J. Tsongalis

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Coleman, W.B., Tsongalis, G.J. (1997). Molecular Mutations in Human Neoplastic Disease. In: Coleman, W.B., Tsongalis, G.J. (eds) Molecular Diagnostics. Pathology and Laboratory Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2588-9_14

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  • DOI: https://doi.org/10.1007/978-1-4757-2588-9_14

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