BRAF inhibitor treatment of melanoma causing colonic polyps: An alternative hypothesis.
World J Gastroenterol
; 23(17): 3022-3029, 2017 May 07.
Article
in En
| MEDLINE
| ID: mdl-28533659
ABSTRACT
Colonic polyps may arise from BRAF inhibitor treatment of melanoma, possibly due to paradoxical activation of the mitogen-activated protein (MAP)-kinase pathway. In an alternative evidence based scenario, tubular colonic adenomas with APC gene mutations have also been identified in the context of BRAF inhibitor treatment, in the absence of mutations of MAPK genes. A minority of colorectal cancers develop by an alternative "serrated polyp pathway". This article postulates a novel hypothesis, that the established phenotypic and molecular characteristics of serrated colonic polyps/CRC offer an intriguing insight into the pathobiology of BRAF inhibitor induced colonic polyps. Serrated polyps are characterized by a CpG island methylation phenotype, MLH1 silencing and cellular senescence. They also have BRAF mutations. The contention is that BRAF inhibitor induced polyps mimic the afore-described histology and molecular features of serrated polyps with the exception that instead of the presence of BRAF mutations they induce C-RAF homodimers and B-RAF C-RAF heterodimers.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Colonic Polyps
/
Adenomatous Polyps
/
MAP Kinase Signaling System
/
Proto-Oncogene Proteins B-raf
/
Melanoma
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
World J Gastroenterol
Journal subject:
GASTROENTEROLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Ireland