Wnt disruption in colorectal polyps - the traditional serrated adenoma enters the fray
The adenoma-carcinoma sequence describes the development of colorectal carcinoma (CRC) from benign colorectal precursor lesions. Molecular classification of established CRC has demonstrated considerable disease heterogeneity; however, as an emerging cancer frequently outgrows and destroys the initia...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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Wiley
2016
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| _version_ | 1797060585776480256 |
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| author | Leedham, S Chetty, R |
| author_facet | Leedham, S Chetty, R |
| author_sort | Leedham, S |
| collection | OXFORD |
| description | The adenoma-carcinoma sequence describes the development of colorectal carcinoma (CRC) from benign colorectal precursor lesions. Molecular classification of established CRC has demonstrated considerable disease heterogeneity; however, as an emerging cancer frequently outgrows and destroys the initial precursor lesion, CRC molecular taxonomy can only be partially reconciled with histologically classified polyps. Thus, the molecular pathogenesis of some colorectal polyp types, including the traditional serrated adenoma (TSA), is still unclear. Now, candidate driver gene analysis of a cohort of different polyps reveals characteristic, but highly variable, mutations disrupting the Wnt signalling pathway across different histological polyp subtypes. How and when different precursor lesions acquire Wnt disruption reflects important distinctions in polyp biology, dependent on a combination of the dominant molecular pathway and the cell of origin of individual lesions. TSAs preferentially acquire ligand-dependent Wnt activating mutations, which means that the cancers that arise from these aggressive polyps may be sensitive to targeted Wnt inhibition. This paper demonstrates that applying next-generation sequencing technology to improve our understanding of colorectal precursor lesion molecular pathogenesis could also give important and translationally relevant insights into colorectal cancer biology. |
| first_indexed | 2024-03-06T20:19:10Z |
| format | Journal article |
| id | oxford-uuid:2d35278d-ac4b-45a0-8d26-48c06a1e455a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:19:10Z |
| publishDate | 2016 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:2d35278d-ac4b-45a0-8d26-48c06a1e455a2022-03-26T12:41:26ZWnt disruption in colorectal polyps - the traditional serrated adenoma enters the frayJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2d35278d-ac4b-45a0-8d26-48c06a1e455aEnglishSymplectic Elements at OxfordWiley2016Leedham, SChetty, RThe adenoma-carcinoma sequence describes the development of colorectal carcinoma (CRC) from benign colorectal precursor lesions. Molecular classification of established CRC has demonstrated considerable disease heterogeneity; however, as an emerging cancer frequently outgrows and destroys the initial precursor lesion, CRC molecular taxonomy can only be partially reconciled with histologically classified polyps. Thus, the molecular pathogenesis of some colorectal polyp types, including the traditional serrated adenoma (TSA), is still unclear. Now, candidate driver gene analysis of a cohort of different polyps reveals characteristic, but highly variable, mutations disrupting the Wnt signalling pathway across different histological polyp subtypes. How and when different precursor lesions acquire Wnt disruption reflects important distinctions in polyp biology, dependent on a combination of the dominant molecular pathway and the cell of origin of individual lesions. TSAs preferentially acquire ligand-dependent Wnt activating mutations, which means that the cancers that arise from these aggressive polyps may be sensitive to targeted Wnt inhibition. This paper demonstrates that applying next-generation sequencing technology to improve our understanding of colorectal precursor lesion molecular pathogenesis could also give important and translationally relevant insights into colorectal cancer biology. |
| spellingShingle | Leedham, S Chetty, R Wnt disruption in colorectal polyps - the traditional serrated adenoma enters the fray |
| title | Wnt disruption in colorectal polyps - the traditional serrated adenoma enters the fray |
| title_full | Wnt disruption in colorectal polyps - the traditional serrated adenoma enters the fray |
| title_fullStr | Wnt disruption in colorectal polyps - the traditional serrated adenoma enters the fray |
| title_full_unstemmed | Wnt disruption in colorectal polyps - the traditional serrated adenoma enters the fray |
| title_short | Wnt disruption in colorectal polyps - the traditional serrated adenoma enters the fray |
| title_sort | wnt disruption in colorectal polyps the traditional serrated adenoma enters the fray |
| work_keys_str_mv | AT leedhams wntdisruptionincolorectalpolypsthetraditionalserratedadenomaentersthefray AT chettyr wntdisruptionincolorectalpolypsthetraditionalserratedadenomaentersthefray |