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

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.
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PMID:High frequency of BRAF mutations in nevi. 1244 72

Melanocortin-1 receptor (MC1R) variants have been associated with BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations in non-CSD (chronic solar-damaged) melanomas in an Italian and an American population. We studied an independent Italian population of 330 subjects (165 melanoma patients and 165 controls) to verify and estimate the magnitude of this association and to explore possible effect modifiers. We sequenced MC1R in all subjects and exon 15 of BRAF in 92/165 melanoma patients. Patients with MC1R variants had a high risk of carrying BRAF mutations in melanomas (odds ratio (OR)=7.0, 95% confidence interval (CI)=2.1-23.8) that increased with the number of MC1R variants and variants associated with red hair color. Combining these subjects with the originally reported Italian population (513 subjects overall), MC1R variant carriers had a 5- to 15-fold increased risk of BRAF-mutant melanomas based on carrying one or two variants (P<0.0001, test for trend), and regardless of signs of chronic solar damage. In contrast, no association with BRAF-negative melanomas was found (OR=1.0, 95% CI=0.6-1.6). No characteristics of subjects or melanomas, including age, nevus count, pigmentation, and melanoma thickness or location on chronically or intermittently sun-exposed body sites, substantially modified this association, although results could be affected by the small numbers in some categories. This study confirms that the known MC1R-melanoma risk association is confined to subjects whose melanomas harbor BRAF mutations.
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PMID:MC1R variants increase risk of melanomas harboring BRAF mutations. 1878 43

Cutaneous melanoma may be quite heterogeneous in its clinical, histologic, and molecular features. Yet, the current classification of melanoma is limited to 4 main subtypes on the basis of clinical and histopathologic features and has shown limited impact on clinical management including prognostication and treatment. Advances in our understanding of the driving molecular pathways in melanoma and the importance of the mitogen-activated protein kinase pathway have shown that specific activating mutations in oncogenes may correlate with characteristic clinical and histologic features. We evaluated 40 melanoma cases with gains in MYC at 8q24, and we show that their characteristic features include aggressive clinical course, occurrence in nonchronically sun-damaged skin, amelanotic clinical and histopathologic appearance, a nodular or primary dermal growth pattern by histology, frequent epidermal consumption, and infrequent association with a precursor nevus. The v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral oncogene homolog (NRAS) mutation status was also determined. The presence of these mutations was comparable to frequencies previously reported from nonchronically sun-damaged skin. However, the BRAF mutant cases did not show histopathologic features considered characteristic of BRAF mutant melanoma. Considering these distinct clinical and histopathologic features and the possible role as a theragnostic tool, it may be of value to consider 8q24 status in cutaneous melanoma in addition to the mutation status of BRAF in future studies integrating molecular findings into the classification system for cutaneous melanoma.
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PMID:Distinctive clinical and histologic features in cutaneous melanoma with copy number gains in 8q24. 2202 39

The activation of RAF-MEK-extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade by v-raf murine sarcoma viral oncogene homolog B1 (BRAF)(V600E) mutation is a key alteration in melanoma. Although BRAF inhibitor (BRAFi) has achieved remarkable clinical success, the positive response to BRAFi is not sustainable, and the initial clinical benefit is eventually barred by the development of resistance to BRAFi. There is growing evidence to suggest that endoplasmic reticulum (ER) stress-induced autophagy could be a potential pro-survival mechanism that contributes to genesis of melanoma and to the resistance to BRAFi. ER stress-induced autophagy is an evolutionarily conserved membrane process. By degrading and recycling proteins and organelles via the formation of autophagous vesicles and their fusion with lysosomes, the autophagy plays a key role in homeostasis as well as pathological processes. In this review, we examine the autophagy phenomenon in melanocytic nevus, primary and metastatic melanoma, and its significance in BRAFi-resistant melanoma.
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PMID:ER stress-induced autophagy in melanoma. 2609 22