Melanoma genetics and the development of rational therapeutics

The Hallmarks of Cancer

2000 • 27,569 citations

Mutations of the BRAF gene in human cancer

2002 • 10,249 citations

BAY 43-9006 Exhibits Broad Spectrum Oral Antitumor Activity and Targets the RAF/MEK/ERK Pathway and Receptor Tyrosine Kinases Involved in Tumor Progression and Angiogenesis

2004 • 3,873 citations

A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4

1993 • 3,680 citations

Cancer Statistics, 2001

2001 • 3,342 citations

Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma

2001 • 2,658 citations

The histogenesis and biologic behavior of primary human malignant melanomas of the skin.

1969 • 2,098 citations

High frequency of BRAF mutations in nevi

2002 • 1,701 citations

ARF Promotes MDM2 Degradation and Stabilizes p53: ARF-INK4a Locus Deletion Impairs Both the Rb and p53 Tumor Suppression Pathways

1998 • 1,584 citations

Role of the INK4a Locus in Tumor Suppression and Cell Mortality

1996 • 1,580 citations

Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19

1997 • 1,568 citations

The Ink4a Tumor Suppressor Gene Product, p19Arf, Interacts with MDM2 and Neutralizes MDM2's Inhibition of p53

1998 • 1,538 citations

Pten is essential for embryonic development and tumour suppression

1998 • 1,507 citations

Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest

1995 • 1,500 citations

Germline p16 mutations in familial melanoma

1994 • 1,241 citations

Model Predicting Survival in Stage I Melanoma Based on Tumor Progression

1989 • 1,235 citations

The alternative product from the human CDKN2A locus, p14ARF, participates in a regulatory feedback loop with p53 and MDM2

1998 • 1,152 citations

A p16 ^INK4a -Insensitive CDK4 Mutant Targeted by Cytolytic T Lymphocytes in a Human Melanoma

1995 • 1,147 citations

Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma

1996 • 1,110 citations

BRAF and RAS mutations in human lung cancer and melanoma.

2002 • 979 citations

A study of tumor progression: The precursor lesions of superficial spreading and nodular melanoma

1984 • 963 citations

Mutation ofPten/Mmac1in mice causes neoplasia in multiple organ systems

1999 • 941 citations

Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2

1998 • 906 citations

High-Dose Interferon Alfa-2b Significantly Prolongs Relapse-Free and Overall Survival Compared With the GM2-KLH/QS-21 Vaccine in Patients With Resected Stage IIB-III Melanoma: Results of Intergroup Trial E1694/S9512/C509801

2001 • 905 citations

Essential role for oncogenic Ras in tumour maintenance

1999 • 880 citations

Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus

1994 • 860 citations

Loss of p16Ink4a with retention of p19Arf predisposes mice to tumorigenesis

2001 • 825 citations

Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma

1996 • 806 citations

Untitled

1996 • 780 citations

Validation of the Accuracy of Intraoperative Lymphatic Mapping and Sentinel Lymphadenectomy for Early-Stage Melanoma

1999 • 774 citations

Prognostic factors in 1,521 melanoma patients with distant metastases.

1995 • 567 citations

Deregulated Akt3 Activity Promotes Development of Malignant Melanoma

2004 • 566 citations

Loss of p16Ink4a confers susceptibility to metastatic melanoma in mice

2001 • 559 citations

Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes.

1986 • 531 citations

Geographical Variation in the Penetrance of CDKN2A Mutations for Melanoma

2002 • 491 citations

Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma.

1997 • 489 citations

Long-Term Results of a Multi-Institutional Randomized Trial Comparing Prognostic Factors and Surgical Results for Intermediate Thickness Melanomas (1.0 to 4.0 mm)

2000 • 478 citations

PTEN signaling pathways in melanoma

2003 • 472 citations

Genetic Interaction Between NRAS and BRAF Mutations and PTEN/MMAC1 Inactivation in Melanoma

2004 • 470 citations

MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.

1997 • 464 citations

B-RAF is a therapeutic target in melanoma

2004 • 435 citations

Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation.

2003 • 432 citations

Discovery of a novel Raf kinase inhibitor.

2001 • 417 citations

Suppression of BRAF(V599E) in human melanoma abrogates transformation.

2003 • 412 citations

Cooperative effects of INK4a and ras in melanoma susceptibility in vivo

1997 • 405 citations

Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France. The French Familial Melanoma Study Group [published erratum appears in Hum Mol Genet 1998 May;7(5):941]

1998 • 387 citations

Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?

2004 • 355 citations

V599EB-RAF is an Oncogene in Melanocytes

2004 • 343 citations

Epidemiology of melanoma

2000 • 343 citations

Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma

1997 • 343 citations

Tumor spectrum in ARF-deficient mice.

1999 • 339 citations

Genetics of melanoma predisposition

2003 • 321 citations

Homozygotes for CDKN2 (p16) germline mutation in Dutch familial melanoma kindreds

1995 • 316 citations

PERSONAL RISK-FACTOR CHART FOR CUTANEOUS MELANOMA

1989 • 310 citations

MC1R Genotype Modifies Risk of Melanoma in Families Segregating CDKN2A Mutations

2001 • 309 citations

BRAF oncogenic mutations correlate with progression rather than initiation of human melanoma.

2003 • 301 citations

The genetics of malignant melanoma: lessons from mouse and man

2003 • 289 citations

Constitutive activation of the Ras-Raf signaling pathway in metastatic melanoma is associated with poor prognosis.

2004 • 281 citations

Ultraviolet radiation and cutaneous malignant melanoma

2003 • 275 citations

A germline deletion of p14ARF but not CDKN2A in a melanoma-neural system tumour syndrome family

2001 • 271 citations

Constitutive activation of Akt/protein kinase B in melanoma leads to up-regulation of nuclear factor-kappaB and tumor progression.

2002 • 256 citations

Kinase Inhibition with BAY 43–9006 in Renal Cell Carcinoma

2004 • 246 citations

Loss of PTEN promotes tumor development in malignant melanoma.

2003 • 243 citations

Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines

1998 • 239 citations

Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines.

2000 • 238 citations

BRAF Mutations Are Common Somatic Events in Melanocytic Nevi11Tables 2 and 3 can be found at http://www.blackwellpublishing.com/products/journals/suppmat/jid/jid22225/jid22225sm.htm

2004 • 232 citations

Mutations of the BRAF Gene in Benign and Malignant Melanocytic Lesions

2003 • 227 citations

Melastatin Expression and Prognosis in Cutaneous Malignant Melanoma

2001 • 219 citations

Analysis of BRAF and N-RAS mutations in metastatic melanoma tissues.

2003 • 215 citations

INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence

2002 • 211 citations

BRAF mutations in metastatic melanoma: a possible association with clinical outcome.

2003 • 208 citations

BRAF alterations are associated with complex mutational profiles in malignant melanoma

2004 • 208 citations

Malignant melanoma: modern black plague and genetic black box

1998 • 198 citations

Analysis of N- and K-Ras Mutations in the Distinctive Tumor Progression Phases of Melanoma

2001 • 180 citations

Absence of BRAF mutations in UV-protected mucosal melanomas

2004 • 180 citations

A melanoma-associated germline mutation in exon 1β inactivates p14ARF

2001 • 173 citations

GM-CSF-secreting melanoma vaccines

2003 • 171 citations

Germ-line deletion involving the INK4 locus in familial proneness to melanoma and nervous system tumors.

1998 • 160 citations

Molecular genetics of familial cutaneous melanoma.

1998 • 159 citations

Mutation and expression of the p53 gene in human malignant melanoma

1994 • 158 citations

Melan-A, A New Melanocytic Differentiation Marker

1999 • 155 citations

BRAF as a potential therapeutic target in melanoma and other malignancies

2003 • 154 citations

Molecular events in melanoma development and progression

1998 • 152 citations

Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice

2002 • 146 citations

BRAF Mutation

2003 • 143 citations

Loss of the p16INK4a and p15INK4b genes, as well as neighboring 9p21 markers, in sporadic melanoma.

1996 • 138 citations

Lack of BRAF Mutation in Primary Uveal Melanoma

2003 • 137 citations

Treatment of metastatic melanoma with an orally available inhibitor of the Ras-Raf-MAPK cascade.

2003 • 132 citations

Components of the Rb pathway are critical targets of UV mutagenesis in a murine melanoma model

2003 • 117 citations

Absence of p53 Gene Mutations in Cutaneous Melanoma

1994 • 114 citations

Prognostic Factors in the Treatment of Cutaneous Melanoma

1979 • 111 citations

Preliminary antitumor activity of BAY 43–9006 in metastatic renal cell carcinoma and other advanced refractory solid tumors in a phase II randomized discontinuation trial (RDT)

2004 • 111 citations

Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma

2004 • 107 citations

Results of phase I pharmacokinetic and pharmacodynamic studies of the Raf kinase inhibitor BAY 43-9006 in patients with solid tumors

2002 • 106 citations

Loss of heterozygosity in sporadic primary cutaneous melanoma

1995 • 102 citations

Loss of heterozygosity for 10q22-10qter in malignant melanoma progression.

1994 • 101 citations

On the antiquity of melanoma

1966 • 101 citations

Case of Fungoid Disease.

1820 • 100 citations

Lack of allelic deletion and point mutation as mechanisms of p53 activation in human malignant melanoma

1993 • 99 citations

Both products of the mouse Ink4a/Arf locus suppress melanoma formation in vivo

2003 • 99 citations

Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity

2003 • 99 citations

In vitro loss of heterozygosity targets the PTEN/MMAC1 gene in melanoma

1998 • 96 citations

The treatment of brain metastases from malignant melanoma

2002 • 94 citations

p53 mutations in human cutaneous melanoma correlate with sun exposure but are not always involved in melanomagenesis

1999 • 85 citations

p53 gene mutation and expression in naevi and melanomas

1995 • 85 citations

Chromosome 10 allelic loss in malignant melanoma

1993 • 83 citations

Novel mutations in the p16/CDKN2A binding region of the cyclin-dependent kinase-4 gene.

1998 • 82 citations

CDKN2A germline splicing mutation affecting both p16^ink4 and p14^arf RNA processing in a melanoma/neurofibroma kindred

2001 • 72 citations

Genetic progression of metastatic melanoma

2004 • 71 citations

p16INK4a inactivation is not frequent in uncultured sporadic primary cutaneous melanoma

1999 • 64 citations

Loss of heterozygosity at chromosome 9p21 (INK4-p14ARF locus)

1999 • 61 citations

Lack ofp53 mutations and loss of heterozygosity in non-cultured human melanocytic lesions

1996 • 59 citations

Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma

2004 • 51 citations

CDKN2A mutation and deletion status in thin and thick primary melanoma.

2000 • 50 citations

Prognostic significance of p53 over-expression in thin melanomas

1995 • 42 citations

Virus, cells and videotape

2002 • 37 citations

Longitudinal Assessment of the Nevus Phenotype in a Melanoma Kindred

2004 • 36 citations

Recent developments in the discovery of protein kinase inhibitors from the urea class.

2004 • 36 citations

Improving Survival in Patients with High-Risk and Metastatic Melanoma

2003 • 33 citations

BAY 43-9006 in patients with advanced melanoma: The Royal Marsden experience

2004 • 31 citations

A phase I clinical and pharmacokinetic study of the Raf kinase inhibitor (RKI) BAY 43-9006 administered in combination with doxorubicin in patients with solid tumors

2003 • 28 citations

Epidemiology, etiology, and control of melanoma.

2001 • 25 citations

Differentiation and metastasis in melanoma.

2000 • 24 citations

Protein kinase inhibitors from the urea class.

2002 • 20 citations