Advances in malignant melanoma: genetic insights from mouse and man.

Notorious for its proclivity for metastases and resistance to known therapies, malignant melanoma represents a major health concern. Genetic, epidemiological and genomic investigations are highlighting a repertoire of stereotypical mutations that are associated with human melanoma genesis. The functional significance of many of these genetic alterations is being ascertained through the use of in vivo mouse models. Insights from human and mouse studies, coupled with the development of novel tools for high-resolution characterization of the melanoma genome, hold promise for the identification of better diagnostic markers and potential therapeutic targets. With the rapid improvements in drug design, these recent advances are generating optimism for the development of better therapeutic options for melanoma patients.

[1]  N. Hayward Genetics of melanoma predisposition , 2003, Oncogene.

[2]  W. Grady Epigenetic events in the colorectum and in colon cancer. , 2005, Biochemical Society transactions.

[3]  L. Chin,et al.  High-resolution characterization of the pancreatic adenocarcinoma genome , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[4]  D. Elder,et al.  UVB induces atypical melanocytic lesions and melanoma in human skin. , 1998, The American journal of pathology.

[5]  C. Eng,et al.  Germline mutations in PTEN are present in Bannayan-Zonana syndrome , 1997, Nature Genetics.

[6]  Peter A. Jones,et al.  The fundamental role of epigenetic events in cancer , 2002, Nature Reviews Genetics.

[7]  W. K. Alfred Yung,et al.  Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers , 1997, Nature Genetics.

[8]  H. Yi,et al.  Suppression of tumorigenicity and metastasis in B16F10 cells by PTEN/MMAC1/TEP1 gene. , 2001, Cancer letters.

[9]  C. Cordon-Cardo,et al.  Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype. , 1989, Oncogene.

[10]  S. Gabriel,et al.  EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy , 2004, Science.

[11]  C. Pirker,et al.  Seven novel and stable translocations associated with oncogenic gene expression in malignant melanoma. , 2005, Neoplasia.

[12]  José Luis de la Pompa,et al.  Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTEN , 1998, Cell.

[13]  P. Demoly,et al.  [Transgenic mice]. , 1992, Annales de dermatologie et de venereologie.

[14]  T. Mak,et al.  High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice , 1998, Current Biology.

[15]  G. Mills,et al.  MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. , 1997, Cancer research.

[16]  L. Chin,et al.  Components of the Rb pathway are critical targets of UV mutagenesis in a murine melanoma model , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Hong Sun,et al.  TEP 1 , Encoded by a Candidate Tumor Suppressor Locus , Is a Novel Protein Tyrosine Phosphatase Regulated by Transforming Growth Factor 1 @ ' , 1997 .

[18]  B. Armstrong,et al.  Cutaneous malignant melanoma and indicators of total accumulated exposure to the sun: an analysis separating histogenetic types. , 1984, Journal of the National Cancer Institute.

[19]  A. Balmain,et al.  Hyperpigmentation and melanocytic hyperplasia in transgenic mice expressing the human T24 HA‐ras gene regulated by a mouse tyrosinase promoter , 1995, Molecular carcinogenesis.

[20]  R. DePinho,et al.  Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth , 1998, Nature.

[21]  M. Martinka,et al.  Prognostic significance of activated Akt expression in melanoma: a clinicopathologic study of 292 cases. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  K. Kinzler,et al.  Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status , 2002, Nature.

[23]  Dean W. Felsher,et al.  Cancer revoked: oncogenes as therapeutic targets , 2003, Nature Reviews Cancer.

[24]  R. DePinho,et al.  Ink 4 a / Arf Deficiency Promotes Ultraviolet Radiation-induced Melanomagenesis 1 , 2002 .

[25]  P. N. Rao,et al.  Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification , 2001, Science.

[26]  G. Merlino,et al.  Accelerated ultraviolet radiation-induced carcinogenesis in hepatocyte growth factor/scatter factor transgenic mice. , 2000, Cancer research.

[27]  L. Mullenders,et al.  UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer. , 2001, Journal of photochemistry and photobiology. B, Biology.

[28]  M. Nelen,et al.  Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. , 1997, Human molecular genetics.

[29]  L. Chin,et al.  Essential role for oncogenic Ras in tumour maintenance , 1999, Nature.

[30]  C. Sawyers,et al.  Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. , 2001, The New England journal of medicine.

[31]  R. Schneider,et al.  UV-induction of keratinocyte endothelin-1 downregulates E-cadherin in melanocytes and melanoma cells. , 2002, The Journal of clinical investigation.

[32]  Daniel Pinkel,et al.  Classifying melanocytic tumors based on DNA copy number changes. , 2003, The American journal of pathology.

[33]  Carlos Cordon-Cardo,et al.  Pten is essential for embryonic development and tumour suppression , 1998, Nature Genetics.

[34]  M. Herlyn,et al.  Shifts in cadherin profiles between human normal melanocytes and melanomas. , 1996, The journal of investigative dermatology. Symposium proceedings.

[35]  D. Haber,et al.  Overcoming Acquired Resistance to Iressa/Tarceva with Inhibitors of a Different Class , 2005, Cell cycle.

[36]  D. Whiteman,et al.  Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies , 2004, Cancer Causes & Control.

[37]  M. Wigler,et al.  PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer , 1997, Science.

[38]  L. Chin,et al.  Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice. , 2002, Nature Reviews Cancer.

[39]  Florence Demenais,et al.  Geographical variation in the penetrance of CDKN2A mutations for melanoma. , 2002, Journal of the National Cancer Institute.

[40]  C. Cordon-Cardo,et al.  Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[41]  D. Elder,et al.  E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. , 2000, The American journal of pathology.

[42]  P. Guldberg,et al.  Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. , 1997, Cancer research.

[43]  C. Berking,et al.  Photocarcinogenesis in human adult skin grafts. , 2002, Carcinogenesis.

[44]  Jing Li,et al.  Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome , 1997, Nature Genetics.

[45]  A. Ray,et al.  Breast and prostate cancer , 2000, Indian Journal of Clinical Biochemistry.

[46]  B. Bastian Understanding the progression of melanocytic neoplasia using genomic analysis: from fields to cancer , 2003, Oncogene.

[47]  J C Briggs,et al.  Cutaneous melanoma. , 1993, Journal of the American Academy of Dermatology.

[48]  W. Cavenee,et al.  In vitro loss of heterozygosity targets the PTEN/MMAC1 gene in melanoma. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[49]  P. Autier,et al.  Influence of sun exposures during childhood and during adulthood on melanoma risk , 1998, International journal of cancer.

[50]  R. Sturm,et al.  Skin colour and skin cancer - the genetic link , 2001 .

[51]  P. Meltzer,et al.  High frequency of BRAF mutations in nevi , 2003, Nature Genetics.

[52]  Patricia L. Harris,et al.  Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. , 2004, The New England journal of medicine.

[53]  P. Duray,et al.  Neonatal sunburn and melanoma in mice , 2001, Nature.

[54]  A. D. Van den Abbeele,et al.  Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. , 2002, The New England journal of medicine.

[55]  T. Ono,et al.  Molecular nature of ultraviolet B light-induced deletions in the murine epidermis. , 2001, Cancer research.

[56]  T. Godfrey,et al.  Gene amplifications characterize acral melanoma and permit the detection of occult tumor cells in the surrounding skin. , 2000, Cancer research.

[57]  A. Nicholson,et al.  Mutations of the BRAF gene in human cancer , 2002, Nature.