Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated the use of pyrosequencing to investigate NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog] mutations in melanoma biopsies. Here, we expanded the analysis to include BRAF (V-raf murine sarcoma viral oncogene homolog B1), another member of the Ras-Raf-mitogen-activated protein kinase (MAPK) signalling pathway, and analysed a total of 294 melanoma tumours from 219 patients. Mutations in BRAF exons 11 and 15 were identified in 156 (53%) tumours and NRAS exon 2 mutations in 86 (29%) tumours. Overall, mutations in NRAS or BRAF were found in 242 of 294 tumours (82%) and were found to be mutually exclusive in all but two cases (0.7%). Multiple metastases were analysed in 57 of the cases and mutations were identical in all except three, indicating that BRAF and NRAS mutations occur before metastasis. Association with preexisting nevi was significantly higher in BRAF mutated tumours (P=0.014). In addition, tumours with BRAF mutations showed a significantly more frequent moderate to pronounced infiltration of lymphocytes (P=0.013). NRAS mutations were associated with a significantly higher Clark level of invasion (P=0.022) than BRAF mutations. Age at diagnosis was significantly higher in tumours with NRAS mutations than in those with BRAF mutations (P=0.019). NRAS and BRAF mutations, however, did not influence the overall survival from time of diagnosis (P=0.7). In conclusion, the separate genotypes were associated with differences in several key clinical and pathological parameters, indicating differences in the biology of melanoma tumours with different proto-oncogene mutations.
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PMID:NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing. 1711 47

Giant congenital melanocytic nevi (CMNs) are at an increased risk for malignant transformation. To explore the mutation frequencies of BRAF(V600E) (V-raf murine sarcoma virus oncogene homolog B1) and NRAS (neuroblastoma ras viral oncogene homolog) codon 61 in CMNs of Chinese, we selected 55 paraffin-embedded tissue blocks, including 37 cases of medium CMNs (1.5-20cm) and 18 cases of giant CMNs (>20 cm). Direct sequencing was performed to detect the BRAF(V600E) and NRAS codon 61 mutations. The BRAF(V600E) mutations were detected in 9 of 55 nevi (16.4%). In medium CMNs, 9 of 37 BRAF(V600E) mutations (24.3%) were detected. Notably, in giant CMNs, no BRAF(V600E) mutations were found. The difference between these frequencies is statistically significant (P = 0.0231). NRAS codon 61 mutations were detected in 13 of 55 nevi (23.6%), including 10 of 37 medium CMNs (27.0%) and 3 of 18 giant CMNs (16.7%). Additionally, the BRAF(V600E) and NRAS codon 61 mutations did not coexist in the same sample. Finally, we found that the NRAS codon 61 mutation was significantly related to the amount of sun exposure (0 of 18 CMNs from sites of intermittent sun exposure and 13 of 36 CMNs from sites of chronic continuous sun exposure, P = 0.0024). The paradoxically higher incidence of BRAF(V600E) mutations in medium-sized compared with giant CMNs suggests that the presence of the BRAF(V600E) mutation may play different roles between medium and giant CMNs in melanocytic tumorigenesis.
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PMID:Lack of BRAF(V600E) mutations in giant congenital melanocytic nevi in a Chinese population. 2143 May 5


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