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World Journal of Surgery

, Volume 16, Issue 2, pp 246–250 | Cite as

Hereditary melanoma and the search for the melanoma gene

  • Richard F. Kefford
World Progress In Surgery

Abstract

The discovery and characterization of growth regulatory genes, in the form of oncogenes, and their counterparts, tumor suppressor (TS) or antioncogenes, has vastly expanded the basic understanding of tumorigenesis. Human solid tumors, such as colorectal cancer, for which the molecular genetics have been most clearly defined, display progressive evolution from cellular dysplasia to anaplasia and metastasis through the stepwise accumulation of genetic defects, involving the regulation and expression of both oncogenes and TS genes. The study of basic genetic abnormalities in melanoma and the identification of the most fundamental of these is critical both to the understanding of abnormal melanocyte proliferation and its potential pharmacologic or immunologic regulation, and also to the identification and screening of patients at high risk for the development of melanoma. The search for such genetic abnormalities has included an analysis of melanomas for defects in known characterized oncogenes and TS genes, and, more importantly, the use of families with hereditary melanoma (HM) and dysplastic nevi in an endeavor to find the melanoma gene. The importance of HM is fundamental, since in the case of other hereditary cancer syndromes for which the genetic basis has been identified, the same or similar genetic abnormalities underlie sporadic tumors of the same tissue type. Thus HM is likely to be the major signpost to the melanomagenic defect.

Keywords

Melanoma Como Cual Basta Hereditary Cancer 
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.

Résumé

La découverte et l'identification des gènes régulateurs de croissance sous forme d'oncogènes et leurs contreparties, les suppresseurs de tumeurs (ST) ou anti-oncogènes ont largement conribué à la compréhension de la tumorigénèse. Les tumeurs solides humaines, tel le cancer colorectal pour lequel la génétique moléculaire a été plus clairement explicite, montrent une évolution progressive allant de la dysplasie cellulaire à l'anaplasie et aux métastases. Cette évolution se produit par l'accumulation, petit à petit, de défauts génétiques portant sur la régulation et l'expression à la fois des oncogènes et des antioncogènes. L'étude des anomalies génétiques dans le mélanome et l'identification des plus essentielles d'entre elles est capitale à la fois pour la compréhension de la prolifération anormale des mélanocytes et de sa régulation potentielle pharmacologique et immunologique et à la fois pour l'identification et le dépistage des patients à haut risque de développer un mélanome. La recherche de telles anomalies génétiques a comporté l'étude, dans le mélanome, de défects au sein d'oncogènes et anti-oncogènes identifiés et, plus important, l'exploitation de familles atteintes de mélanome héréditaire (HM) et de naevi dysplasiques dans le but de trouver le gène du mélanome. L'étude du mélanome héréditaire est fondamentale car dans le cas d'autres syndromes de cancers héréditaires où les bases génétiques ont été identifiées, des anomalies génétiques identiques ou comparables sont a la base des tumeurs sporadiques de même type tissulaire. Aussi le HM semble être le meilleur indicateur du défaut de la mélanogénèse.

Resumen

El descubrimiento y la caracterización de genes reguladores del crecimiento celular, en la forma de oncogenes, y sus contrapartes, los supresores tumorales (ST), o antioncogenes, ha ampliado en forma considerable el conocimiento básico del proceso de tumorogénesis. Los tumores sólidos humanos, tales como el cáncer colorrectal, en el cual se ha logrado definir con la mayor claridad la genética molecular, exhiben una evolución progresiva desde la displasia celular basta la anaplasia y las metástasis a través de la acumulación secuencial de alteraciones genéticas, involucrando la regulación y la expresión tanto de oncogenes como de genes ST. El estudio de las anormalidades genéticas básicas en el melanoma y la identificación de aquellas más fundamentales es crítico, tanto para la comprensión de la proliferación melanocítica anormal, y su potencial regulación farmacológica o inmunológica, como para la indentificación y tamizaje de pacientes de alto riesgo de desarrollar melanoma. La búsqueda de tales anormalidades genéticas ha incluido el análisis de melanomas para identificar defectos en genes conocidos como oncogenes y genes ST, y, aún más importante el nevus displásicos en un esfuerzo por hallar el gen del melanoma. La importancia del melanoma hereditario es fundamental, puesto que en otros síndromes de cáncer hereditario en los cuales se ha identificado la base genética, se encuentran las mismas, o similares, anormalidades genéticas en tumores esporádicos del mismo tipo tisular. Por lo tanto, el melanoma hereditario probablemente sea un indicador del defecto melanocítico.

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References

  1. 1.
    Lynch, H.T., Fusaro, R.M., Kimberling, W.J., Lynch, J.F., Danes, B.S.: Familial atypical multiple mole-melanoma (FAMMM) syndrome: Segregation analysis. J. Med. Genet.20:342, 1983PubMedGoogle Scholar
  2. 2.
    Greene, M.H., Clark, W.H.J., Tucker, M.A., Kraemer, K.H., Elder, D.E., Fraser, M.C.: The high risk of malignant melanoma in melanoma-prone families with dysplastic nevi. Ann. Intern. Med.102:458, 1985PubMedGoogle Scholar
  3. 3.
    Tucker, M.A., Bale, S.J.: Clinical aspects of familial cutaneous malignant melanoma. Semin. Oncol.15:524, 1988PubMedGoogle Scholar
  4. 4.
    Greene, M.H., Clark, W.H., Tucker, M.A., Elder, D.E., Kraemer, K.H., Guerry, D.P.I., Witmer, W.K., Thompson, J., Matozzo, I., Fraser, M.C.: Acquired precursors of cutaneous malignant melanoma: The familial dysplastic nevus syndrome. N. Engl. J. Med.312:91, 1985PubMedGoogle Scholar
  5. 5.
    Kefford, R.F., Salmon, J., Shaw, H.M., Donald, J.A., McCarthy, W.H.: Hereditary melanoma in Australia: Variable association with dysplastic nevi and absence of genetic linkage to chromosome 1p. Cancer Genet. Cytogenet.51:45, 1990Google Scholar
  6. 6.
    English, D.R., Armstrong, B.K.: Identifying people at high risk of cutaneous malignant melanoma: Results from a case-control study in Western Australia. Br. Med. J.296:1285, 1988Google Scholar
  7. 7.
    Holman, C.D., Armstrong, B.K.: Pigmentary traits, ethnic origin, benign nevi, and family history as risk factors for cutaneous malignant melanoma. J. Natl. Cancer Inst.72:257, 1984PubMedGoogle Scholar
  8. 8.
    Ackerman, A.B., Mihara, I.: Dysplasia, dysplastic melanocytes, dysplastic nevi, the dysplastic nevus syndrome, and the relation between dysplastic nevi and malignant melanomas. Hum. Pathol.16:87, 1985PubMedGoogle Scholar
  9. 9.
    Meyer, L.J., Piepkorn, M.W., Seuchter, S.A., Cannon-Albright, L.A., Bishop, D.T., Zone, J.J., Skolnick, M.H.: Genetic and epidemiologic evaluation of dysplastic nevi. Pigment Cell Res. Suppl.1:144, 1988Google Scholar
  10. 10.
    Elder, D.E.: Dysplastic nevus syndrome: Biological significance. Semin. Oncol.15:529, 1988PubMedGoogle Scholar
  11. 11.
    Rigel, D.S., Rivers, J.K., Kopf, A.W., Friedman, R.J., Vinokur, A.F., Heilman, E.R., Levenstein, M.: Dysplastic nevi: Markers for increased risk for melanoma. Cancer63:386, 1989PubMedGoogle Scholar
  12. 12.
    Piepkorn, M., Meyer, L.J., Goldgar, D., Seuchter, S.A., Cannon-Albright, L.A., Skolnick, M.H.: The dysplastic melanocytic nevus: A prevalent lesion that correlates poorly with clinical phenotype. J. Am. Acad. Dermatol.20:407, 1989.PubMedGoogle Scholar
  13. 13.
    Bale, S.J., Chakravarti, A., Greene, M.H.: Cutaneous malignant melanoma and familial dysplastic nevi: Evidence for autosomal dominance and pleiotropy. Am. J. Hum. Genet.38:188, 1986PubMedGoogle Scholar
  14. 14.
    Dracopoli, N.C., Bale, S.J.: Genetic aspects of cutaneous malignant melanoma. Semin. Oncol.15:541, 1988PubMedGoogle Scholar
  15. 15.
    Srivastava, S., Zou, Z.Q., Pirollo, K., Blattner, W., Chang, E.H.: Germ-line transmission of a mutated P53 gene in a cancer-prone family with Li-Fraumeni Syndrome. Nature348:747, 1990PubMedGoogle Scholar
  16. 16.
    Viskochil, D., Buchberg, A.M., Xu, G., Cawthon, R.M., Stevens, J., Wolff, R.K., Culver, M., Carey, J.C., Copeland, N.G., Jenkins, N.A., White, R., O'Connell, P.: Deletions and a translocation interrupt a cloned gene at the Neurofibromatosis Type 1 locus. Cell62:187, 1990PubMedGoogle Scholar
  17. 17.
    Hall, J.M., Lee, M.K., Newman, B., Morrow, J.E., Anderson, L.A., Huey, B., King, M.C.: Linkage of early-onset familial breast cancer to chromosome-17Q21. Science250:1684, 1990PubMedGoogle Scholar
  18. 18.
    Ott, J.: Analysis of Human Genetic Linkage, Baltimore, Johns Hopkins University Press, 1985, pp. 1–223Google Scholar
  19. 19.
    Weber, J.L., May, P.E.: Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am. J. Hum. Genet.44:388, 1989PubMedGoogle Scholar
  20. 20.
    Genetic Analysis Workshop 7: Issues in gene mapping and detection of major genes. In Cytogenetics and Cell Genetics, J.W. MacCluer, A. Chakra varti, D. Cox, D.T. Bishop, S.J. Bale, M.H. Skolnick, editors, Basel, S. Karger (in press)Google Scholar
  21. 21.
    Lu, S.-J., Day, N.E., Degos, L., Lepage, V., Wang, P.-C., Chan, S.-H., Simons, M., McKnight, B., Easton, D., Zeng, Y., de-The, G.: Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region. Nature346:470, 1990PubMedGoogle Scholar
  22. 22.
    Bale, S.J., Dracopoli, N.C., Tucker, M.A., Clark, W.H.J., Fraser, F.C., Stanger, B.Z., Green, P., Donis-Keller, H., Greene, M.H., Housman, D.E.: Mapping the gene for hereditary cutaneous malignant melanoma/dysplastic nevus to chromosome 1p. N. Engl. J. Med.320:1367, 1989PubMedGoogle Scholar
  23. 23.
    van Haeringen, A., Bergman, W., Nelen, M.R., van der Kooig-Meijs, Henrikse, I., Wejnes, J.H., Kahn, P.M., Klasen, E.C., Frantz, R.: Exclusion of dysplastic nevus syndrome locus from the short arm of chromosome 1 in Dutch families. Genomics5:61, 1989PubMedGoogle Scholar
  24. 24.
    Cannon-Albright, L.A., Goldgar, D.E., Wright, E.C., Turco, A., Jost, M., Meyer, L.J., Piepkorn, M., Zone, J.J., Skolnick, M.H.: Evidence against the reported linkage of the cutaneous melanoma-dysplastic nevus syndrome locus to chromosome 1p36. Am. J. Hum. Genet.46:912, 1990PubMedGoogle Scholar
  25. 25.
    Dracopoli, N.C., Harnett, P., Bale, S.J., Stanger, B.Z., Tucker, M.A., Housman, D.E., Kefford, R.F.: Loss of alleles from the distal short arm of chromosome 1 occurs late melanoma tumor progression. Proc. Natl. Acad. Sci.86:4614, 1989PubMedGoogle Scholar
  26. 26.
    Harnett, P., Kefford, R.F.: Molecular models of tumorigenesis: Application to familial and sporadic melanoma. Semin. Oncol.15:549, 1988PubMedGoogle Scholar
  27. 27.
    Hecht, F., Hecht, B.K.-M.: Chromosome rearrangements in dysplastic nevus syndrome predisposing to malignant melanoma. Cancer Genet. Cytogenet.35:73, 1988PubMedGoogle Scholar
  28. 28.
    McCowan, J., Halaban, R., Francke, U.: Cytogenetic analysis of melanocytes from premalignant nevi and melanomas. J. Natl. Cancer Inst.80:1159, 1988PubMedGoogle Scholar
  29. 29.
    Richmond, A., Fine, R., Murray, D., Hawson, D., Priest, J.H.: Growth factor and cytogenetic abnormalities in cultured nevi and malignant melanomas. J. Invest. Dermatol.86:295, 1986PubMedGoogle Scholar
  30. 30.
    Trent, J.M., Thompson, F.H., Meyskens, F.L.: Identification of a recurring translocation site involving chromosome 6 in human malignant melanoma. Cancer Res.49:420, 1989PubMedGoogle Scholar
  31. 31.
    Dasgupta, P., Linnenbach, A.J., Giaccia, A.J., Stamato, T.D., Reddy, E.P.: Molecular cloning of the breakpoint region on chromosome 6 in cutaneous malignant melanoma: Evidence for deletion in the c-myb locus and translocation of a segment of chromosome 12. Oncogene4:1201, 1989PubMedGoogle Scholar
  32. 32.
    Trent, J.M., Stanbridge, E.J., McBride, H.L., Meese, E.U., Casey, G., Araujo, D.E., Witkowski, C.M., Nagle, R.B.: Tumorigenicity in human melanoma cell lines controlled by introduction of human chromosome 6. Science247:568, 1990PubMedGoogle Scholar
  33. 33.
    Specht, C.S., Smith, T.W.: Uveal malignant melanoma and von Recklinghausen's neurofibromatosis. Cancer62:812, 1988PubMedGoogle Scholar
  34. 34.
    To, K.W., Rabinowitz, S.M., Friedman, A.H., Merker, C., Cavanaugh, C.P.: Neurofibromatosis and neural crest neoplasms: Primary acquired melanosis and malignant melanoma of the conjunctiva. Surv. Ophthalmol.33:373, 1989PubMedGoogle Scholar
  35. 35.
    Antle, C.M., Damji, K.F., White, V.A., Rootman, J.: Uveal malignant melanoma and optic nerve glioma in von Recklinghausen's neurofibromatosis. Br. J. Ophthalmol.74:502, 1990PubMedGoogle Scholar
  36. 36.
    Rutten, A., Goos, M.: Nevus spilus with malignant melanoma in a patient with neurofibromatosis (letter). Arch. Dermatol.126:539, 1990Google Scholar
  37. 37.
    Baldini, M.T., Belli, F., Leo, E., Bartoli, C., Rovati, M., Rovati, L., Veronesi, P.: Von Recklinghausen disease and cutaneous melanoma: A rare association. G. Ital. Oncol.8:93, 1988PubMedGoogle Scholar
  38. 38.
    Silverman, J.F., Blahove, M., Collins, J.L., Norris, H.T.: Cutaneous malignant melanoma in a black patient with neurofibromatosis (von Recklinghausen's disease). Am. J. Dermatopathol.10:536, 1988PubMedGoogle Scholar
  39. 39.
    Miyauchi, T., Maruoka, M., Nagayama, T.: Malignant melanoma of the penis associated with von Recklinghausen's neurofibromatosis: Report of a case. Hinyokika Kiyo34:710, 1988PubMedGoogle Scholar
  40. 40.
    Chenevix-Trench, G., Martin, N.G., Ellem, K.A.: Gene expression in melanoma cell lines and cultured melanocytes: Correlation between levels of c-src-1, c-myc and p53. Oncogene5:1187, 1990PubMedGoogle Scholar
  41. 41.
    Shin, D.M., Gupta, V., Donner, L., Chawla, S., Benjamin, R., Gutterman, J., Blick, M.: Aberrant oncogene expression in uncultured human sarcoma and melanoma. Anticancer Res.7:1117, 1987PubMedGoogle Scholar
  42. 42.
    Westermark, B., Johnsson, A., Paulsson, Y., Betsholtz, C., Heldin, C.H., Herlyn, M., Rodeck, U., Koprowski, H.: Human melanoma cell lines of primary and metastatic origin express the genes encoding the chains of platelet-derived growth factor (PDGF) and produce a PDGF-like growth factor. Proc. Natl. Acad. Sci.83:7197, 1986PubMedGoogle Scholar
  43. 43.
    Albino, A.P., Nanus, D.M., Mentle, I.R., Cordon-Cardo, C., McNutt, N.S., Bressler, J., Andreeff, M.: Analysis of ras oncogenes in malignant melanoma and precursor lesions: Correlation of point mutations with differentiation phenotype. Oncogene4:1363, 1989PubMedGoogle Scholar
  44. 44.
    Raybaud, F., Noguchi, T., Marics, I., Adelaide, J., Planche, J., Batoz, M., Aubert, C., de Lapeyriere, O., Birnbaum, D.: Detection of a low frequency of activated ras genes in human melanomas using a tumorigenicity assay. Cancer Res.48:950, 1988PubMedGoogle Scholar
  45. 45.
    Hotta, H., Ross, A.H., Huebner, K., Isobe, M., Wendeborn, S., Chao, M.V., Ricciardi, R.P., Tsujimoto, Y., Croce, C.M., Koprowski, H.: Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression. Cancer Res.48:2955, 1988PubMedGoogle Scholar
  46. 46.
    Hecht, F., Hecht, B.K.-M.: Chromosome rearrangements in dysplastic nevus syndrome predisposing to malignant melanoma. Cancer Genet. Cytogenet.35:73, 1988PubMedGoogle Scholar
  47. 47.
    Herlyn, M., Clark, W.H., Rodeck, U., Mancianti, M.L., Jambrosic, J., Koprowski, H.: Biology of tumor progression in human melanocytes. Lab. Invest.56:461, 1987PubMedGoogle Scholar
  48. 48.
    Stanbridge, E.J.: Human tumor suppressor genes. Annu. Rev. Genet.24:615, 1990PubMedGoogle Scholar
  49. 49.
    Cooper, J.A., Whyte, P.: RB and cell cycle: Entrance or exit? Cell58:1009, 1989PubMedGoogle Scholar
  50. 50.
    Weinberg, R.: The Rb gene and the negative regulation of cell growth. Blood74:529, 1989PubMedGoogle Scholar
  51. 51.
    Stanbridge, E.J., Nowell, P.C.: Origins of cancer revisited. Cell63:867, 1990PubMedGoogle Scholar
  52. 52.
    Howe, J.A., Mymryk, J.S., Egan, C., Branton, P.E., Bayley, S.T.: Retinoblastoma growth suppressor and a 300-kDa protein appear to regulate cellular DNA synthesis. Proc. Natl. Acad. Sci.87:5883, 1990PubMedGoogle Scholar
  53. 53.
    Lin, B.T.Y., Gruenwald, S., Morla, A.O., Lee, W.H., Wang, J.Y.J.: Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase. EMBO J.10:857, 1991PubMedGoogle Scholar
  54. 54.
    Traboulsi, E.I., Zimmerman, L.E., Manz, H.J.: Cutaneous malignant melanoma in survivors of heritable retinoblastoma. Arch. Ophthalmol.106:1059, 1988PubMedGoogle Scholar
  55. 55.
    Hayasaka, S., Mizuno, K.: Malignant melanoma of the choroid in a mother and retinoblastoma in her son. Br. J. Ophthalmol.70:107, 1986PubMedGoogle Scholar
  56. 56.
    Nigro, J.M., Baker, S.J., Preisinger, A.C., Jessup, J.M., Hostetter, R., Cleary, K., Bigner, S.H., Davidson, N., Baylin, S., Devilee, P., Glover, T., Collins, F.S., Weston, A., Modali, R., Harris, C., Vogelstein, B.: Mutations in the p53 gene occur in diverse human tumour types. Nature342:705, 1989PubMedGoogle Scholar
  57. 57.
    Iggo, R., Gatter, K., Bartek, J., Lane, D., Harris, A.: Increased expression of mutant forms of p53 oncogene in primary lung cancer. Lancet335:675, 1990PubMedGoogle Scholar
  58. 58.
    Bodmer, W.F., Bailey, C.J., Bodmer, J., Bussey, H.J.R., Ellis, A., Gorman, P., Lucibello, F.C., Murday, V.A., Rider, S.H., Scambler, P., Sheer, D., Solomon, E., Spurr, N.K.: Localization of the gene for familial adenomatous polyposis on chromosome 5. Nature328:614, 1987PubMedGoogle Scholar
  59. 59.
    Solomon, E.: Colorectal cancer genes. Nature343:412, 1990PubMedGoogle Scholar
  60. 60.
    Seizinger, B.R., Rouleau, G.A., Ozelius, L.J., 28 others.: Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature332:268, 1988PubMedGoogle Scholar
  61. 61.
    Anders, F., Anders, A.: Etiology of cancer as studied in the platyfishswordtail system. Biochim. Biophys. Acta516:61, 1978PubMedGoogle Scholar
  62. 62.
    Wittbrodt, J., Adam, D., Malitschek, B., Mauler, W., Raulf, F., Telling, A., Robertson, S.M., Schartl, M.: Novel putative receptor tyrosine kinase encoded by the melanoma-inducing Tu locus in Xiphophorus. Nature341:415, 1989PubMedGoogle Scholar

Copyright information

© the Société Internationale de Chirurgie 1992

Authors and Affiliations

  • Richard F. Kefford
    • 1
  1. 1.Department of Medical OncologyThe University of Sydney, Westmead CentreAustralia

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