Figure 5 the arf p53 and p16ink4a rb path ways ras

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Unformatted text preview: e ARF-p53 and p16INK4A-RB path ways . RAS cooperates with RB pathway and affect cell cycle progression by upregulating Cyclin D, CDK4, and/or Cyclin E/CDK2, whi ch ultimately inactivate RB. Mutations in oncogenes and suppressor genes in melanoma: The molecular genetic alterations during melanoma development are partially characterized. Mutations in many different genes, such as NRAS, BRAF and PTEN and mutations and deletions of CDKN2A have all been implicated in the pathogenesis 13 of malignant melanoma. Selected genetic alterations in malignant melanomas are summarized in table 1(25). Table 1 : Genetic alterations in malignant melano ma. Modified from Dohmem et al . 2007. Gene type Gene Oncogenes BRAF NRAS AKT3 CCND1 MITF CD KN2 A Alteration f requency in melanoma 5 0 -7 0 % 1 5 -3 0 % 4 3 -6 0 % 6 -4 4 % 1 0 -1 6 % 3 0 -7 0 % PTEN APAF-1 P53 2 0 -4 0 % 40% 10% Tumor suppressors Alteration type(s) mutation mutation overexpression amplification amplification deletion, mu tation or silencing deletion or mu tation silencing loss or mutation RAS: RAS genes are among the most frequently mutated genes in human cancers, but display distinct spectra of mutations of NRAS, HRAS, and KRAS in different malignancies. Human melanomas carry mutations almost exclusively in NRAS (536%), with 90% of mutations localized to codon 61 (28-30). HRAS and KRAS are much less frequently mutated. NRAS mutations are found in approximately 10% of common acquired nevi (31, 32) and it was recently determined that 81% (26/32) of congenital nevi harbor mutations in NRAS, while BRAF mutations were absent in such lesions (33). Albino et al have reported that 24% of cultured metastatic and 12% of noncultured primary and metastatic melanomas carry NRAS alterations, although others reported higher frequencies in primary tumors and have suggested that mutations correlate with metastasis or disease progression (34). In one study, however 33% of primary and 26% of metastatic melanoma samples were found to harbor mutations in the NRAS gene (35, 36). Activating NRAS mutations...
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This document was uploaded on 03/06/2014.

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