INT132521

Context Info Confidence 0.65 First Reported 2006 Last Reported 2010 Negated 1 Speculated 1 Reported most in Body Documents 14 Total Number 15 Disease Relevance 13.59 Pain Relevance 0.73

cytosol (BRAF) plasma membrane (BRAF) nucleus (BRAF) cytoplasm (BRAF)

Anatomy Link Frequency thyroid 1 colon 1 MLH1 1 BRAF (Homo sapiens)

Pain Link Frequency Relevance Heat melanocortin 1 receptor 5 100.00 Opioid 1 89.12 Glutamate 2 88.96 metalloproteinase 4 68.00 antagonist 5 58.40 Kinase C 1 39.56 palliative 5 25.36 agonist 8 5.00 cINOD 5 5.00 Pain 3 5.00

Disease Link Frequency Relevance Heat Sarcoma 2 100.00 Colon Cancer 213 99.84 Microsatellite Instability 21 99.80 Nevus 3 99.80 Cancer 468 99.60 Ovarian Cancer 6 99.16 Hereditary Nonpolyposis Colorectal Neoplasms 22 98.76 Skin Cancer 79 98.28 Melanoma 119 98.22 Thyroid Neoplasm 162 97.96

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Genetic alterations such as the p16(INK4a) deletion, melanocortin 1 receptor (MC1R), RAS, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) may be indicative of a predisposition to melanoma development.

Gene_expression (deletion) of BRAF associated with sarcoma, melanocortin 1 receptor and skin cancer

1) Confidence 0.65 Published 2007 Journal Mol. Carcinog. Section Abstract Doc Link 17570501 Disease Relevance 0.80 Pain Relevance 0.10

Mutations of BRAF were shown to be absent in UMs [95, 99].

Gene_expression (Mutations) of BRAF

2) Confidence 0.59 Published 2010 Journal Dermatology Research and Practice Section Body Doc Link PMC2902045 Disease Relevance 0.65 Pain Relevance 0

Since elevated activation of the RAS signaling pathway, including overexpression of HER-2/neu and mutations of RAS and BRAF, is common in human ovarian carcinoma, we examined the cellular effect of oncogenic RAS on the expression status of OPCML in a genetically defined human ovarian cancer model.

Gene_expression (overexpression) of BRAF associated with ovarian cancer

3) Confidence 0.58 Published 2006 Journal FASEB J. Section Abstract Doc Link 16384911 Disease Relevance 0.47 Pain Relevance 0.09

Likewise, in our cohort of 14 congenital nevi, we also detected four with BRAF mutations, all heterozygous V600E.

Gene_expression (detected) of BRAF associated with nevus

4) Confidence 0.57 Published 2010 Journal J Transl Med Section Body Doc Link PMC2917408 Disease Relevance 0.84 Pain Relevance 0

Loss of heterozygosity, BRAF and KRAS mutations and microsatellite instability analysis

Gene_expression (mutations) of BRAF associated with microsatellite instability

5) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997072 Disease Relevance 0.34 Pain Relevance 0.03

Other molecular alterations such as KRAS and BRAF mutations do not seem to be associated with PPARG methylation, while a correlation with the microsatellite instability status was found (Figure S1) [10].

Gene_expression (mutations) of BRAF associated with microsatellite instability

6) Confidence 0.52 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2997072 Disease Relevance 0.81 Pain Relevance 0

Since this initial report, Xing has shown that the BRAF activating mutation is the most common genetic alteration in thyroid cancer (Xing 2005), occurring in 18% to 87% of thyroid cancers (Trovisco et al 2006); importantly, the BRAFV600E mutation occurs in nearly 45% of sporadic cases of PTC (Xing 2005) and 24% of cases of anaplastic carcinoma (Salvatore et al 2006).

Gene_expression (activating) of BRAF in thyroid associated with thyroid neoplasm

7) Confidence 0.52 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2621417 Disease Relevance 1.25 Pain Relevance 0.14

In sporadic MSI cases of colon cancer this mutation is found in proximal colon tumors with MLH1 methylation (80% of cases), while in tumors from hereditary nonpolyposis colorectal cancer (HNPCC) cases with MLH1, MSH2 or MSH6 germline mutations, no BRAF mutations are detected.

Neg (no) Gene_expression (detected) of BRAF in MLH1 associated with cancer, colon cancer and hereditary nonpolyposis colorectal neoplasms

8) Confidence 0.51 Published 2008 Journal Current Genomics Section Body Doc Link PMC2674304 Disease Relevance 1.49 Pain Relevance 0

They also showed that 90% of serrated polyps that showed dysplasia had mutations in BRAF or k-ras and that these acquired mutations were mutually exclusive, i.e. either BRAF or k-ras was present.

Gene_expression (present) of BRAF associated with cleidocranial dysplasia and polyps

9) Confidence 0.39 Published 2008 Journal Current Genomics Section Body Doc Link PMC2674304 Disease Relevance 1.70 Pain Relevance 0

Recent publications have shown that the KRAS and BRAF mutation status of colon cancer cells influence the expression rates of multiple proliferative as well as apoptotic signaling intermediates (Kikuchi et al, Cancer Res 2009, Oliveira et al, Oncogene 2003, Seruca et al, 2009), including HIF1?

Gene_expression (status) of BRAF in colon associated with cancer, colon cancer and apoptosis

10) Confidence 0.26 Published 2010 Journal BMC Cancer Section Body Doc Link PMC3003660 Disease Relevance 1.70 Pain Relevance 0

Genetic alterations such as the p16(INK4a) deletion, melanocortin 1 receptor (MC1R), RAS, and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) may be indicative of a predisposition to melanoma development.

Gene_expression (deletion) of viral oncogene homolog B1 associated with sarcoma, melanocortin 1 receptor and skin cancer

11) Confidence 0.19 Published 2007 Journal Mol. Carcinog. Section Abstract Doc Link 17570501 Disease Relevance 0.80 Pain Relevance 0.10

DROSHA, ITGB4, IGF1R, MT1X, MT1E, BRAF) was likewise affected by Par-4 overexpression in HT29 cells (Figure 2A; see Additional file 2 for gene symbols and their corresponding gene names).

Gene_expression (overexpression) of BRAF

12) Confidence 0.18 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2883962 Disease Relevance 0.52 Pain Relevance 0

Melanomas collected from 123 Australian patients were analyzed for melanocortin-1 receptor (MC1R) variants and mutations in the BRAF and NRAS genes.

Spec (analyzed) Gene_expression (variants) of BRAF associated with melanocortin 1 receptor and melanoma

13) Confidence 0.14 Published 2010 Journal J. Invest. Dermatol. Section Abstract Doc Link 19571821 Disease Relevance 1.11 Pain Relevance 0.26

Reduced levels of c-Myc and phosphorylated c-Raf protein suggest the disruption of Ras-dependent signaling by HPGGT.

Gene_expression (levels) of c-Raf protein

14) Confidence 0.06 Published 2007 Journal Gastroenterology Section Body Doc Link 17484877 Disease Relevance 0 Pain Relevance 0

Components of these pathways include genes such as Ras, B-Raf, PI3K, PTEN and Akt that can be mutated or aberrantly expressed in human cancer.

Gene_expression (expressed) of B-Raf associated with cancer

15) Confidence 0.06 Published 2009 Journal Mol Cancer Section Body Doc Link PMC2777152 Disease Relevance 1.11 Pain Relevance 0

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