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PubMed:16585161 JSONTXT

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PubmedHPO

Id	Subject	Object	Predicate	Lexical cue
T1	325-347	HP_0004808	denotes	acute myeloid leukemia
T2	331-347	HP_0012324	denotes	myeloid leukemia
T3	339-347	HP_0001909	denotes	leukemia
T4	1316-1322	HP_0002664	denotes	cancer
T5	1487-1492	HP_0002664	denotes	tumor

DisGeNET5_variant_disease

Id	Subject	Object	Predicate	Lexical cue
16585161-3#41#46#geners767580335	499-504	geners767580335	denotes	I448V
16585161-3#31#36#geners730881002	489-494	geners730881002	denotes	S427G
16585161-3#97#100#diseaseC0023467	555-558	diseaseC0023467	denotes	AML
41#46#geners76758033597#100#diseaseC0023467	16585161-3#41#46#geners767580335	16585161-3#97#100#diseaseC0023467	associated_with	I448V,AML
31#36#geners73088100297#100#diseaseC0023467	16585161-3#31#36#geners730881002	16585161-3#97#100#diseaseC0023467	associated_with	S427G,AML

DisGeNET5_gene_disease

Id	Subject	Object	Predicate	Lexical cue
16585161-2#134#139#gene673	441-446	gene673	denotes	B-RAF
16585161-0#17#22#gene5894	17-22	gene5894	denotes	C-RAF
16585161-0#71#109#diseaseC1336735	71-109	diseaseC1336735	denotes	therapy-related acute myeloid leukemia
16585161-2#18#40#diseaseC0023467	325-347	diseaseC0023467	denotes	acute myeloid leukemia
16585161-2#42#45#diseaseC0023467	349-352	diseaseC0023467	denotes	AML
16585161-3#4#9#gene5894	462-467	gene5894	denotes	C-RAF
16585161-3#142#146#gene2322	600-604	gene2322	denotes	FLT3
16585161-3#97#100#diseaseC0023467	555-558	diseaseC0023467	denotes	AML
17#22#gene589471#109#diseaseC1336735	16585161-0#17#22#gene5894	16585161-0#71#109#diseaseC1336735	associated_with	C-RAF,therapy-related acute myeloid leukemia
134#139#gene67318#40#diseaseC0023467	16585161-2#134#139#gene673	16585161-2#18#40#diseaseC0023467	associated_with	B-RAF,acute myeloid leukemia
134#139#gene67342#45#diseaseC0023467	16585161-2#134#139#gene673	16585161-2#42#45#diseaseC0023467	associated_with	B-RAF,AML
4#9#gene589497#100#diseaseC0023467	16585161-3#4#9#gene5894	16585161-3#97#100#diseaseC0023467	associated_with	C-RAF,AML
142#146#gene232297#100#diseaseC0023467	16585161-3#142#146#gene2322	16585161-3#97#100#diseaseC0023467	associated_with	FLT3,AML

2015-BEL-Sample-2

Id	Subject	Object	Predicate	Lexical cue
BEL:20039216	0-1507	kin(p(MGI:Raf1)) decreases bp(GOBP:"apoptotic process")	denotes	Two transforming C-RAF germ-line mutations identified in patients with therapy-related acute myeloid leukemia. Mutations leading to activation of the RAF-mitogen-activated protein kinase/extracellular signal-regulated (ERK) kinase (MEK)-ERK pathway are key events in the pathogenesis of human malignancies. In a screen of 82 acute myeloid leukemia (AML) samples, 45 (55%) showed activated ERK and thus were further analyzed for mutations in B-RAF and C-RAF. Two C-RAF germ-line mutations, S427G and I448V, were identified in patients with therapy-related AML in the absence of alterations in RAS and FLT3. Both exchanges were located within the kinase domain of C-RAF. In vitro and in vivo kinase assays revealed significantly increased activity for (S427G)C-RAF but not for (I448V)C-RAF. The involvement of the S427G C-RAF mutation in constitutive activation of ERK was further confirmed through demonstration of activating phosphorylations on C-RAF, MEK, and ERK in neoplastic cells, but not in nonneoplastic cells. Transformation and survival assays showed oncogenic and antiapoptotic properties for both mutations. Screening healthy individuals revealed a <1/400 frequency of these mutations and, in the case of I448V, inheritance was observed over three generations with another mutation carrier suffering from cancer. Taken together, these data are the first to relate C-RAF mutations to human malignancies. As both mutations are of germ-line origin, they might constitute a novel tumor-predisposing f

DisGeNET

Id	Subject	Object	Predicate	Lexical cue
T0	1375-1380	gene:5894	denotes	C-RAF
T1	1400-1412	disease:C0006826	denotes	malignancies
R1	T0	T1	associated_with	C-RAF,malignancies