A novel transforming gene in a human malignant melanoma cell line

Padua, Rose Ann; Barrass, Nigel; Currie, G. A.

doi:10.1038/311671a0

Cited by 119 publications

(54 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40,41 Because BRAF mutations confer RAS-independent activation of the MAP kinase pathway, it is not surprising that NRAS and BRAF mutations are mutually exclusive. 42,43 There is significant overlap between BRAF mutation and p16 deletion or mutation in melanoma.…”

Section: Genetic Alterations Beyond Braf In Melanomamentioning

confidence: 99%

BRAF, a target in melanoma

Flaherty

McArthur

2010

Cancer

111

View full text Add to dashboard Cite

The successful translation of therapies targeting signal-transduction pathways that are activated by oncogenes has provided a model for molecularly targeted therapy, and the identification of mutations in v-raf murine sarcoma viral oncogene homolog B1 (BRAF), a serine/threonine kinase, has turned the attention of the melanoma field toward this concept. The current review indicated that BRAF represents an important target in cancer, in part because it is present in 7% of all cancers and also because it represents the first intracellular signaling molecule that is activated by point mutations for which single-agent therapy appears to have efficacy. Therapy for advanced melanoma has progressed slowly over the past 3 decades, although significant advances have been made in other cancers with the application of cytotoxic chemotherapy and targeted therapies. However, in melanoma, cytotoxic chemotherapies have severe limits, chemotherapy does not convincingly improve on the natural history of metastatic disease and has no role in the adjuvant setting, and cytokine therapy may have a niche in both the adjuvant and metastatic settings but confers only a modest benefit to a small proportion of patients at the cost of severe toxicity. Thus, there are few other cancers in which completely novel therapies are so highly prioritized in clinical research. Understanding network of signal-transduction pathways and how that network may adapt to BRAF inhibition or mitogen-activated protein kinase kinase inhibition will point to the next generation of clinical trials investigating rational combination regimens. The current investigations in melanoma will create a set of hypotheses to be tested in each cancer that harbors BRAF mutations. Cancer 2010;116:4902-13. V C 2010 American Cancer Society.KEYWORDS: BRAF, melanoma, oncogene, kinase inhibitor, mutation.Therapy for advanced melanoma has progressed slowly over the past 3 decades, whereas significant advances have been made with the application of cytotoxic chemotherapy and, more recently, targeted therapies in other cancers. The application of cytotoxic chemotherapies that have disease-altering ability in other cancers has severe limits in melanoma. Chemotherapy does not convincingly improve upon the natural history of metastatic disease and has no role in the adjuvant setting. Cytokine therapy has a niche in both the adjuvant and metastatic settings but confers a modest benefit to a small proportion of patients at the cost of severe toxicity. Thus, there are few other cancers in which completely novel therapies are so highly prioritized in clinical research. The successful translation of therapies targeting signal-transduction pathways that are activated by oncogenes has provided a model for molecularly targeted therapy. The identification of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in 2002 was the watershed event that turned the attention of the melanoma field to this concept. 1 BRAF BiologyRaf kinases are components of the mitogen-activated protein (MAP) k...

show abstract

Section: Genetic Alterations Beyond Braf In Melanomamentioning

confidence: 99%

BRAF, a target in melanoma

Flaherty

McArthur

2010

Cancer

111

View full text Add to dashboard Cite

show abstract

“…Genetic studies of melanoma-prone kindreds indicate a highly penetrant, autosomal, dominant mode of inheritance for a dysplastic nevus syndrome/CMM-susceptibility gene with provisional linkage to the Rh locus on the short arm of chromosome 1 (7,8). Experimental transformation of mouse NIH 3T3 cells with human melanoma DNA has detected the sporadic activation of the oncogenes HRAS (9, 10), NRAS (10,11), and the RAS-related gene MEL (12,13). Cytogenetic studies of melanoma cell cultures have revealed nonrandom chromosomal alterations most frequently involving chromosomes 1, 6, and 7 (14-20).…”

mentioning

confidence: 99%

Structural alteration in the MYB protooncogene and deletion within the gene encoding alpha-type protein kinase C in human melanoma cell lines.

Linnenbach

Huebner

Reddy

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…1 and 2). However, a variety of other genes-including B-lym (3), met (4), NK 14 (5), mcf-2 and mcf-3 (6), neu (7), dbl (8), ret (9), raf (10), and trk (11)-have also been identified. Products of several of these transforming genes appear to be structurally related to those of the tyrosine kinase family of oncogenes (11)(12)(13)(14).…”

mentioning

confidence: 99%

Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

Srivastava¹,

Wheelock²,

Aaronson³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The dbl oncogene was initially isolated from a human diffuse B-cell lymphoma. Antisera from mice bearing tumors induced by this oncogene specifically detected a protein of about 66 kDa (p66) in dbl transformants. dbl cDNA-selected poly(A)I RNA isolated from a transfectant clone expressing p66 directed the in vitro synthesis of this protein, establishing that it is encoded by dbl. Subcellulat localization studies revealed that p66 is a cytoplasmic protein distributed between cytosol and crude membrane fractions. Moreover, p66 was shown to be a phosphoprotein, with phosphorylation specific to serine residues. Our characterization of the dbl-encoded protein appears to distinguish this transforming gene product from those of other known oncogenes.

show abstract

A novel transforming gene in a human malignant melanoma cell line

Cited by 119 publications

References 28 publications

BRAF, a target in melanoma

BRAF, a target in melanoma

Structural alteration in the MYB protooncogene and deletion within the gene encoding alpha-type protein kinase C in human melanoma cell lines.

Identification of the protein encoded by the human diffuse B-cell lymphoma (dbl) oncogene.

Contact Info

Product

Resources

About