Abstract
During the last 20–30 years, a large body of epidemiologic, cytogenetic, and experimental studies have supported the hypothesis that tumors are caused by genetic damage. The recent advances in molecular biology have definitively proved that this hypothesis was correct, and at present there is no doubt that the basic lesion of the malignant cell is an abnormality in the DNA structure or sequence which results in uncontrolled growth. Two particular classes of genes have been identified — oncogenes and tumor suppressor genes — which are of major importance in the initiation and progression of human malignancies [1].
Keywords
- Tumor Suppressor Gene
- Familial Adenomatous Polyposis
- Adenomatous Polyposis Coli
- Multiple Endocrine Neoplasia Type
- Burkitt Lymphoma
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
The striking advances in cancer genetics during the past fifteen years have made it clear that the root causes of this disease are linked to malfunctioning genes. R. A. Weinberg (1992)
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References
Weinberg RA (1992) The integration of molecular genetics into cancer management. Cancer 70:1653–1658
Slamon DJ (1987) Proto-oncogenes and human cancers. N Engl J Med 317: 955–957
Rous PA (1911) A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13:397–411
Santos E, Tronik SR, Aaronson SA et al. (1982) T24 human bladder carcinoma oncogene is an activated form of the normal human homologue of BALB and Harvey-MSV transforming genes. Nature 298:343–347
Reddy EP, Reynolds RK, Santos E et al. (1992) A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300:149–152
Stacey DW, Kung HF (1984) Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein. Nature 310:508–511
Little GD, Nau MM, Carney DN et al. (1983) Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature 306:194–196
Dalla-Favera R, Bregni M, Erikson J et al. (1982) Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci USA 79:7824–7827
Bishop JM (1991) Molecular themes in oncogenesis. Cell 64:235–248
Harris H, Klein G (1969) Malignancy of somatic cell hybrids. Nature 224: 1314–1316
Stanbridge EJ (1990) Identifying tumor suppressor genes in human colorectal cancer. Science 247:12–13
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767
Knudson A (1977) Genetics and the etiology of human cancer. Adv Hum Genet 8:1–66
Lee WH, Bookstein R, Hong F et al. (1987) Human retinoblastoma susceptibility gene: cloning identification, and sequence. Science 235:1394–1399
Friend SH, Bernards R, Rogeli S et al. (1986) A human DNA segment with properties of the gene that predisposes to retino-blastoma and osteosarcoma. Nature 323:643–646
Benedict WF, Srivatsan ES, Mark C et al. (1987) Complete or partial homo-zygosity of chromosome 13 in primary retinoblastoma. Cancer Res 47:4189–4191
Bunin GR, Beverly SE, Meadows AT et al. (1989) Frequency of 13q abnormalities among 203 patients with retinoblastoma. J Natl Cancer Inst 81:370–374
Weinberg RA (1989) Oncogenes, antioncogenes and the molecular bases of multistep carcinogenesis. Cancer Res 49:3713–3721
Weinberg RA (1991) Tumor suppressor genes. Science 254:1138–1146
Lee EYHP, Chang CY, Hu N et al. (1992) Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359:288–294
Jacks T, Fazeli A, Schmitt EM et al. (1992) Effect of an Rb mutation in the mouse. Nature 359:295–300
Eeles AE (1993) Predictive testing for germline mutations in the p53 gene: are all the questions answered? Eur J Cancer 29A: 1361–1365
Malkin D, Jolly KW, Barbier N et al. (1992) Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med 326:1309–1315
Toguchida J, Yamaguchi T, Dayton SH et al. (1992) Prevalence and spectrum of germline mutations of the p53 gene among patients with sarcoma. N Engl J Med 326:1301–1308
Levine AJ, Momand J, Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456
Nigro JM, Baker SJ, Presinger AC et al. (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708
Baker SJ, Fearon ER, Nigro JM et al. (1989) Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244:217–221
Coles C, Condie A, Chetty U et al. (1992) p53 mutations in breast cancer. Cancer Res 52:5291–5298
Nigro JM, Baker SJ, Presinger AC et al. (1989) Mutations in the p53 gene occur in diverse human tumor types. Nature 342:705–708
Hinds P, Finlay CA, Quartin RS et al. (1990) Mutant p53 DNA clones from human colon carcinomas cooperate with ras in transforming primary rat cells: a comparison of the “hot spot” mutant phenotypes. Cell Growth Differ 1:571–580
Dittmer D, Pati S, Zambetti G et al. (1993) Gain of function mutations in p53. Nature Genetics 4:42–45
Soussi T, Caron de Fromentel C, May P (1990) Structural aspects of the p53 protein in relation to gene evolution. Oncogene 5:945–952
Mitsudomi T, Steinberg SM, Nau MM et al. (1992) p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene 7:171–180
Bressac B, Kew M, Wands J (1991) Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature 350:429–431
Ozturk M (1991) p53 mutation in hepatocellular carcinoma after aflatoxin exposure. Lancet 358:1356–1359
Scorsone KA, Zhou YZ, Butel JS et al. (1992) p53 mutations cluster at codon 249 in hepatitis B virus-positive hepatocellular carcinomas from China. Cancer Res 52:1635–1638
Cunningham J, Lust JA, Schaid DJ et al. (1992) Expression of p53 and 17p allelic loss in colorectal carcinoma. Cancer Res 52:1974–1980
Hollstein M, Sidransky D, Vogelstein B et al. (1991) p53 mutations in human cancer. Science 253:49–53
Donehower LA, Harvey M, Slagle BL et al. (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356: 215–221
Hunter T (1991) Cooperative between oncogenes. Cell 64:249–270
Land H, Parada LF, Weinberg RA (1983) Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304: 596–602
Levine AJ, Momand J (1990) Tumor suppressor genes: the p53 and retino-blastoma genes and gene products. Biochim Biophys Acta 1032:119–136
Finlay CA, Hinds PW, Levine AJ (1989) The p53 protooncogene can act as a suppressor of tranformation. Cell 57:1083–1093
Hamilton SR (1993) The molecular genetics of colorectal neoplasia. Gastro-enterology 105:3–7
Kinzler KW, Nilbert MC, Su LK et al. (1991) Identification of FAP locus genes from chromosome 5q21. Science 253:661–665
Groden J, Thilveris A, Samowitz W et al. (1991) Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589–600
Kinzler K, Nilbert MC, Vogelstein B et al. (1991) Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science 251:1366–1370
Deschner EE (1988) Cell proliferation and colonic neoplasia. Scand J Gastro-enterol 23[Suppl l]:94–97
Ponz de Leon M, Roncucci L, Di Donato P et al. (1988) Pattern of epithelial cell proliferation in colorectal mucosa of normal subjects and of patients with adenomatous polyps or cancer of the large bowel. Cancer Res 48:4121–4126
Cohn KH, Wang F, DeSoto-LaPaix F et al. (1991) Association of nm23-Hl allelic deletions with distant metastases in colorectal carcinoma. Lancet 338: 722–724
Bülow S (1989) Familial adenomatous polyposis. Ann Med 21:299–307
Lyons J, Landis CA, Harsh G et al. (1990) Two G protein oncogenes in human endocrine tumors. Science 249:655–659
Brandi ML (1991) Multiple endocrine neoplasia type 1: general features and new insights into etiology. J Endocrinol Invest 14:61–72
Scott N, Quirke P (1993) Molecular biology of colorectal neoplasia. Gut 34: 298–292
Itoh F, Hinoda Y, Ohe M et al. (1993) Decreased expression of DCC mRNA in human colorectal cancers. Int J Cancer 53:260–263
Mulligan LM, Kwok JB, Healey CS et al. (1993) Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363: 458–460
Pezzella F, Turley H, Kuzu I et al. (1993) bcl-2 protein in non-small-cell lung carcinoma. N Engl J Med 329:690–694
Wang L, Patel U, Ghosh L et al. (1993) Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res 53:717–720
Kinzler KW, Vogelstein B (1993) A gene for neurofibromatosis 2. Nature 363:495–496
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© 1994 Springer-Verlag Berlin Heidelberg
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de Leon, M.P. (1994). Oncogenes and Tumor Suppressor Genes. In: Familial and Hereditary Tumors. Recent Results in Cancer Research, vol 136. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85076-9_4
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DOI: https://doi.org/10.1007/978-3-642-85076-9_4
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