Molecular Events in the Development and Progression of Medullary Thyroid Cancer and Pheochromocytoma

Part of the Medical Intelligence Unit book series (MIU.LANDES)


Alterations in several classes of genes can contribute to the development and progression of tumors. These abnormalities can be classified into three general groups: dominant oncogenes, tumor suppressor genes, and genetic instability genes. This chapter reviews what is known about abnormalities in these classes of genes in MTC and pheochromocytoma.


Medullary Thyroid Carcinoma Multiple Endocrine Neoplasia Type Medullary Thyroid Medullary Thyroid Cancer Tumor Suppressor Locus 
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  1. 1.
    Fearon ER, Vogelstein B. A genetic model for colorectal tumori-genesis. Cell 1990; 61: 759–67.PubMedCrossRefGoogle Scholar
  2. 2.
    Moley J, Wallin G, Brother M et al. Oncogene and growth factor expression in MEN related tumors. Henry Ford Hospital Medical Journal 1992; 40: 284–8.PubMedGoogle Scholar
  3. 3.
    Roncalli M, Viale G, Grimelius L et al. Prognostic value of N-myc immunoreactivity in medullary thyroid carcinoma. Cancer 1994; 74: 134–41.PubMedCrossRefGoogle Scholar
  4. 4.
    Moley JF, Brother MB, Wells SA Jr et al. Low frequency of ras gene mutations in neuroblastomas, pheochromocytomas, and medullary thyroid cancers. Cancer Research 1991; 51: 1596–9.PubMedGoogle Scholar
  5. 5.
    Cavenee WK, Dryja TP, Phillips RA et al. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 1983; 305: 779–84.PubMedCrossRefGoogle Scholar
  6. 6.
    Mathew CGP, Smith BA, Thorpe K et al. Deletion of genes on chromosome 1 in endocrine neoplasia. Nature 1987; 328: 524–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Mulligan LM, Gardner E, Smith BA et al. Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2. Genes, Chromosomes and Cancer 1993; 6: 166–7.CrossRefGoogle Scholar
  8. 8.
    Landsvater RM, Mathew CG, Smith BA et al. Development of multiple endocrine neoplasia type 2A does not involve substantial deletions of chromosome 10. Genomics 1989; 4: 246–50.PubMedCrossRefGoogle Scholar
  9. 9.
    Nelkin BD, Nakamura Y, White RW et al. Low incidence of loss of chromosome 10 in sporadic and hereditary human medullary thyroid carcinoma. Cancer Research 1989; 49: 4114–9.PubMedGoogle Scholar
  10. 10.
    Khosla S, Patel VM, Hay ID et al. Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas. Journal of Clinical Investigation 1991; 87: 1691–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Moley J, Brother M, Fong C et al. Consistent association of 1p loss of heterozygosity with pheochromocytomas from patients with multiple endocrine neoplasia type 2 syndromes. Cancer Research 1992; 52: 770–4.PubMedGoogle Scholar
  12. 12.
    Shin E, Fujita S, Takami K et al. Deletion mapping of chromosome 1p and 22q in pheochromocytoma. Japanese Journal of Cancer Research 1993; 84: 402–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Moley JF, Marshall HN. 1p Deletions in human pheochromocytomas share a common pericentromeric breakpoint and do not involve imprinting. American Journal of Human Genetics 1994; 55: A347.Google Scholar
  14. 14.
    Moley JF, Marshall MN, Gagliardi G et al. Loss of heterozygosity of 1p is an early event in the development of pheochromocytomas from patients with multiple endocrine neoplasia types 2A and 2B. Proceedings of the American Association for Cancer Research 1995; 36: A3265.Google Scholar
  15. 15.
    Dou S, Toshima K, Liu L et al. Identification of chromosomal loci for tumor suppressor loci implicated in progression of pheochromocytoma and medullary thyroid carcinoma. American Journal of Human Genetics 1994; 55: A20.Google Scholar
  16. 16.
    Lum S, Brodeur G, Wells S et al. Loss of heterozygosity at the p53 (17p13) locus in human pheochromocytomas. Proceedings of the American Society of Human Genetics 1992: A244.Google Scholar
  17. 17.
    Yoshimoto K, Iwahana H, Fukuda A et al. Role of p53 mutations in endocrine tumorigenesis: mutation detection by polymerase chain reaction-single strand conformation polymorphism. Cancer Research 1992; 52: 5061–4.PubMedGoogle Scholar
  18. 18.
    Yana I, Nakamura T, Shin E et al. Inactivation of the p53 gene is not required for tumorigenesis of medullary thyroid carcinoma or pheochromocytoma. Japanese Journal of Cancer Research 1992; 83: 1113–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Lin SR, Lee YJ, Tsai JH. Mutations of the p53 gene in human functional adrenal neoplasms. Journal of Clinical Endocrinolology and Metabolism 1994; 78: 483–91.CrossRefGoogle Scholar
  20. 20.
    Latif F, Tory K, Gnarra J et al. Identification of the von HippelLindau disease tumor suppressor gene. Science 1993; 260: 1317–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Duan DR, Pause A, Burgess WH et al. Inhibition of transcription elongation by the VHL tumor suppressor protein. Science 1995; 269: 1402–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Aso T, Lane WS, Conaway JW, Conaway RC. Elongin (SIII): A multisubunit regulator of elongation by RNA polymerase II. Science 1995; 269: 1439–43.PubMedCrossRefGoogle Scholar
  23. 23.
    Kibel A, Iliopoulos O, DeCaprio JA et al. Binding of the von Hippel-Lindau tumor suppressor protein to elongin B and C. Science 1995; 269: 1444–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Krumm A, Groudine M. Tumor suppression and transcription elongation: the dire consequences of changing partners. Science 1995; 269: 1400–1.PubMedCrossRefGoogle Scholar
  25. 25.
    Crossey PA, Richards FM, Foster K et al. Identification of intragenic mutations in the von Hippel-Lindau disease tumor suppressor gene and correlation with disease phenotype. Human Mol Genetics 1994; 3: 1303–8.CrossRefGoogle Scholar
  26. 26.
    Gnarra JR, Tory K, Weng Y et al. Mutations of the VHL tumor suppressor gene in renal carcinoma. Nature Genetics 1994; 7: 85–90.PubMedCrossRefGoogle Scholar
  27. 27.
    Gutmann DH, Geist RT, Rose K et al. Loss of neurofibromatosis type I (NF1) gene expression in pheochromocytomas from patients without NF1. Genes, Chromosomes and Cancer 1995; 13: 104–9.CrossRefGoogle Scholar
  28. 28.
    Xu G, O’Connell P, Viskochil D et al. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 1990; 62: 599–608.PubMedCrossRefGoogle Scholar
  29. 29.
    Xu G, Lin B, Tanaka K et al. The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell 1990; 63: 835–41.PubMedCrossRefGoogle Scholar
  30. 30.
    Li Y, Bollag G, Clark R et al. Somatic mutations in the neurofibromatosis 1 gene in human tumors. Cell 1992; 69: 275–81.PubMedCrossRefGoogle Scholar
  31. 31.
    Viskochil D, White R, Cawthon R. The neurofibromatosis type 1 gene. Annu Rev Neurosci 1993; 16: 183–205.PubMedCrossRefGoogle Scholar
  32. 32.
    McCormick F. Ras signaling and NF1. Current Opinion in Genetics and Development 1995; 5: 51–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Traverse S, Gomez N, Paterson H et al. Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor. Biochem J 1992; 288: 351–5.PubMedGoogle Scholar
  34. 34.
    Bootsma D, Weeda G, Vermeulen W et al. Nucleotide excision repair syndromes: molecular basis and clinical symptoms. Philos Trans R Soc Lond B Biol Sci 1995; 347: 75–81.PubMedCrossRefGoogle Scholar
  35. 35.
    Kolodner RD, Hall NR, Lipford J et al. Human mismatch repair genes and their association with hereditary non-polyposis colon cancer. Cold Spring Harb Symp Quant Biol 1994; 59: 331–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Liu B, Parsons R, Papadopoulos N et al. Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nature Medicine 1996; 2: 169–74.PubMedCrossRefGoogle Scholar
  37. 37.
    Yang KP, Nguyen CV, Castillo SG et al. Deletion mapping on the distal third region of chromosome 1 p in multiple endocrine neoplasia type IIA. Anticancer Research 1990; 10: 527–33.PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1996

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