BRAF inhibitor treatment of melanoma causing colonic polyps: An alternative hypothesis
| Autor: | Hazel O’Sullivan, Grainne Callaghan, Fergal C. Kelleher, Catriona Gallagher |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Proto-Oncogene Proteins B-raf endocrine system diseases MAP Kinase Signaling System Adenomatous Polyposis Coli Protein Colonic Polyps Context (language use) Gene mutation Biology MLH1 Frontier Epigenesis Genetic 03 medical and health sciences Adenomatous Polyps 0302 clinical medicine medicine otorhinolaryngologic diseases Gene silencing Humans Gene neoplasms Melanoma Cellular Senescence Serrated polyps Malignant melanoma Gastroenterology BRAF inhibitors General Medicine DNA Methylation medicine.disease Phenotype digestive system diseases Proto-Oncogene Proteins c-raf 030104 developmental biology 030220 oncology & carcinogenesis Mutation Cancer research CpG Islands Mitogen-Activated Protein Kinases Protein Multimerization Colorectal Neoplasms MutL Protein Homolog 1 |
| Zdroj: | World Journal of Gastroenterology |
| ISSN: | 2219-2840 1007-9327 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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