Mutational analysis of the BRAF gene in human congenital and dysplastic melanocytic naevi

Papp, Thilo; Schipper, Holger; Kumar, Krishan; Schiffmann, Dietmar; Zimmermann, R.

doi:10.1097/00008390-200510000-00008

Cited by 57 publications

(52 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a former study, by analysing 18 CMN and 18 DMN lesions, we could not demonstrate a single alteration in either one of these genes (44). In agreement with our results, Kumar et al (41) found no p16 INK4a mutations in 27 investigated commonly acquired melanocytic naevi.…”

Section: Discussionsupporting

confidence: 91%

Mutational analysis of Chk1, Chk2, Apaf1 and Rb1 in human malignant melanoma cell lines

et al. 2007

Self Cite

View full text Add to dashboard Cite

Abstract. Four tumour suppressor genes (Chk1, Chk2, Apaf1 and Rb1) in nine human malignant melanoma cell lines were screened for a loss of gene expression, point mutations and small deletions/insertions by cDNA-based DGGE/SCCP analysis. In two cell lines alterations of the investigated genes could be demonstrated. This result confirms our assumption of the participation of dysfunctional p53 inducer/effector genes in human melanoma aetiology. Furthermore, it points towards the probable principal role of diverse alternative p53-pathway disruption mechanisms in this highly therapy-resistant malignancy without affecting p53 itself. To our knowledge, this is the first CHK1/CHK2 mutation screening in human melanoma.

show abstract

Section: Discussionsupporting

confidence: 91%

Mutational analysis of Chk1, Chk2, Apaf1 and Rb1 in human malignant melanoma cell lines

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…30,31 Therefore, based on the above genetic analysis, we speculated that IDH mutation confers a growth advantage after acquiring BRAF or KIT mutation. Because the functional significance of IDH2 mutations detected in this study remains in need of further characterization, we focused on biological roles of a well-characterized IDH1 mutation (R132H) in melanoma.…”

Section: Mutant Idh1-expressing Melanoma Cells Confer a Growth Advantmentioning

confidence: 99%

Mutant IDH1 Confers an in Vivo Growth in a Melanoma Cell Line with BRAF Mutation

Shibata¹,

Kokubu²,

Miyamoto³

et al. 2011

The American Journal of Pathology

117

View full text Add to dashboard Cite

Melanoma is the most deadly tumor of the skin, and systemic therapies for the advanced stage are still limited. Recent genetic analyses have revealed the molecular diversity of melanoma and potential therapeutic targets. By screening a cohort of 142 primary nonepithelial tumors, we discovered that about 10% of melanoma cases (4/39) harbored an IDH1 or IDH2 mutation. These mutations were found to coexist with BRAF or KIT mutation, and all IDH1 mutations were detected in metastatic lesions. BRAF-mutated melanoma cells, additionally expressing the cancer-related IDH1 mutant, acquired increased colony-forming and in vivo growth activities and showed enhanced activation of the MAPK and STAT3 pathways. Genome-wide gene expression profiling demonstrated that mutant IDH1 affected the expression of a set of genes. Especially, it caused the induction of growth-related transcriptional regulators (Jun, N-myc, Atf3) and the reduction of Rassf1 and two dehydrogenase genes (Dhrs1 and Adh5), which may be involved in the carcinogenesis of IDH1-mutated tumors. Our analyses demonstrate that IDH1 mutation works with other oncogenic mutations and could contribute to the metastasis in melanoma. Melanoma is the most malignant tumor of the skin, and the median survival rate of patients with metastatic tumors is less than 1 year.1 Although the incidence of melanoma has been increasing around the world, systemic therapies for the advanced stage are still limited. 2Recent studies have provided a clearer picture of the molecular events leading to melanoma development and progression.3,4 Since the identification of prevalent activating mutations of BRAF kinase, 5 further molecular studies have clarified the role of this pathway and others in melanomagenesis. 6 Recent genetic investigations have also demonstrated specific genotype-phenotype correlations that would be potentially informative in the context of the molecular subclassification of melanoma and therapeutic target molecules.7 For example, the c-kit gene mutations have been frequently reported in acral lentiginous/mucosal melanomas and are associated with better responsiveness to the inhibitor, imatinib. -10Recently, unbiased whole-exon resequencing analysis of glioblastoma multiforme has revealed recurrent mutation of the two IDH (isocitrate dehydrogenase) isoforms, IDH1 and IDH2.11 Subsequent analysis showed that these mutations are frequent in glioma and associated with better prognosis 12,13 ; furthermore, they have also been detected in a subset (about 8% to 16%) of acute myeloid leukemia (AML).14 -17 These enzymes convert isocitrate to ␣-ketoglutarate (␣-KG) with concurrent reduction of NADPH, but IDH1 is localized in the cytosol 18 whereas IDH2 is localized in mitochondria. 19 Mutations of the two genes affect the residues responsible for hydrophilic interactions with the substrate, and have been shown to impair the enzymatic activity, and therefore they are considered to be loss-of-function alleles.12 However, because the mutations are clustered in specific residues and only...

show abstract

“…Although BRAF mutations are frequently present in common acquired naevi, their prevalence in congenital naevi (which are present at birth) is less clear. Several groups have reported BRAF mutations in congenital naevi (Davies et al, 2002;Yazdi et al, 2003;Michaloglou et al, 2005;Papp et al, 2005). Others however, did not detect them in congenital naevi of medium to large size and in giant congenital naevi, some of which harbour NRAS mutations (De Raeve et al, 2006;Bauer et al, 2007).…”

Section: Activating Braf Mutations In Melanocytic Naevi and Other Benmentioning

confidence: 99%

BRAFE600 in benign and malignant human tumours

et al. 2007

View full text Add to dashboard Cite

Of the RAF family of protein kinases, BRAF is the only member to be frequently activated by mutation in cancer. A single amino acid substitution (V600E) accounts for the vast majority and results in constitutive activation of BRAF kinase function. Its expression is required to maintain the proliferative and oncogenic characteristics of BRAF E600 -expressing human tumour cells. Although BRAF E600 acts as an oncogene in the context of additional genetic lesions, in primary cells it appears to be associated rather with transient stimulation of proliferation. Eventually, BRAF E600 signalling triggers cell cycle arrest with the hallmarks of cellular senescence, as is illustrated by several recent studies in cultured cells, animal models and benign human lesions. In this review, we will discuss recent advances in our understanding of the role of BRAF E600 in benign and malignant human tumours and the implications for therapeutic intervention.

show abstract

Mutational analysis of the BRAF gene in human congenital and dysplastic melanocytic naevi

Cited by 57 publications

References 28 publications

Mutational analysis of Chk1, Chk2, Apaf1 and Rb1 in human malignant melanoma cell lines

Mutational analysis of Chk1, Chk2, Apaf1 and Rb1 in human malignant melanoma cell lines

Mutant IDH1 Confers an in Vivo Growth in a Melanoma Cell Line with BRAF Mutation

BRAFE600 in benign and malignant human tumours

Contact Info

Product

Resources

About