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Comprehensive Mutation Analysis in Colorectal Flat Adenomas

BACKGROUND: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phe...

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Autores principales: Voorham, Quirinus J. M., Carvalho, Beatriz, Spiertz, Angela J., Claes, Bart, Mongera, Sandra, van Grieken, Nicole C. T., Grabsch, Heike, Kliment, Martin, Rembacken, Bjorn, van de Wiel, Mark A., Quirke, Philip, Mulder, Chris J. J., Lambrechts, Diether, van Engeland, Manon, Meijer, Gerrit A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407043/
https://www.ncbi.nlm.nih.gov/pubmed/22848674
http://dx.doi.org/10.1371/journal.pone.0041963
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author Voorham, Quirinus J. M.
Carvalho, Beatriz
Spiertz, Angela J.
Claes, Bart
Mongera, Sandra
van Grieken, Nicole C. T.
Grabsch, Heike
Kliment, Martin
Rembacken, Bjorn
van de Wiel, Mark A.
Quirke, Philip
Mulder, Chris J. J.
Lambrechts, Diether
van Engeland, Manon
Meijer, Gerrit A.
author_facet Voorham, Quirinus J. M.
Carvalho, Beatriz
Spiertz, Angela J.
Claes, Bart
Mongera, Sandra
van Grieken, Nicole C. T.
Grabsch, Heike
Kliment, Martin
Rembacken, Bjorn
van de Wiel, Mark A.
Quirke, Philip
Mulder, Chris J. J.
Lambrechts, Diether
van Engeland, Manon
Meijer, Gerrit A.
author_sort Voorham, Quirinus J. M.
collection PubMed
description BACKGROUND: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phenotypes. METHODS: A consecutive series of 106 flat and 93 polypoid adenomas was analyzed retrospectively for frequently occurring mutations in “hot spot” regions of KRAS, BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (β-catenin), EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high-throughput genotyping technique. Additionally, APC was analyzed using direct sequencing. RESULTS: APC mutations were more frequent in polypoid adenomas compared to flat adenomas (48.5% versus 30.3%, respectively, p = 0.02). Mutations in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST-G) no differences were observed for any of the investigated genes. CONCLUSION: The lower APC mutation rate in flat adenomas compared to polypoid adenomas suggests that disruption of the Wnt-pathway may occur via different mechanisms in these two phenotypes. Furthermore, in contrast to previous observations our results in this large well-defined sample set indicate that there is no significant association between the different morphological phenotypes and mutations in key genes of the RAS-RAF-MAPK pathway.
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spelling pubmed-34070432012-07-30 Comprehensive Mutation Analysis in Colorectal Flat Adenomas Voorham, Quirinus J. M. Carvalho, Beatriz Spiertz, Angela J. Claes, Bart Mongera, Sandra van Grieken, Nicole C. T. Grabsch, Heike Kliment, Martin Rembacken, Bjorn van de Wiel, Mark A. Quirke, Philip Mulder, Chris J. J. Lambrechts, Diether van Engeland, Manon Meijer, Gerrit A. PLoS One Research Article BACKGROUND: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a distinct biology and a more aggressive clinical behavior compared to their polypoid counterparts. In the present study, we aimed to compare the mutation spectrum of 14 cancer genes, between these two phenotypes. METHODS: A consecutive series of 106 flat and 93 polypoid adenomas was analyzed retrospectively for frequently occurring mutations in “hot spot” regions of KRAS, BRAF, PIK3CA and NRAS, as well as selected mutations in CTNNB1 (β-catenin), EGFR, FBXW7 (CDC4), PTEN, STK11, MAP2K4, SMAD4, PIK3R1 and PDGFRA using a high-throughput genotyping technique. Additionally, APC was analyzed using direct sequencing. RESULTS: APC mutations were more frequent in polypoid adenomas compared to flat adenomas (48.5% versus 30.3%, respectively, p = 0.02). Mutations in KRAS, BRAF, NRAS, FBXW7 and CTNNB1 showed similar frequencies in both phenotypes. Between the different subtypes of flat adenomas (0-IIa, LST-F and LST-G) no differences were observed for any of the investigated genes. CONCLUSION: The lower APC mutation rate in flat adenomas compared to polypoid adenomas suggests that disruption of the Wnt-pathway may occur via different mechanisms in these two phenotypes. Furthermore, in contrast to previous observations our results in this large well-defined sample set indicate that there is no significant association between the different morphological phenotypes and mutations in key genes of the RAS-RAF-MAPK pathway. Public Library of Science 2012-07-27 /pmc/articles/PMC3407043/ /pubmed/22848674 http://dx.doi.org/10.1371/journal.pone.0041963 Text en © 2012 Voorham et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Voorham, Quirinus J. M.
Carvalho, Beatriz
Spiertz, Angela J.
Claes, Bart
Mongera, Sandra
van Grieken, Nicole C. T.
Grabsch, Heike
Kliment, Martin
Rembacken, Bjorn
van de Wiel, Mark A.
Quirke, Philip
Mulder, Chris J. J.
Lambrechts, Diether
van Engeland, Manon
Meijer, Gerrit A.
Comprehensive Mutation Analysis in Colorectal Flat Adenomas
title Comprehensive Mutation Analysis in Colorectal Flat Adenomas
title_full Comprehensive Mutation Analysis in Colorectal Flat Adenomas
title_fullStr Comprehensive Mutation Analysis in Colorectal Flat Adenomas
title_full_unstemmed Comprehensive Mutation Analysis in Colorectal Flat Adenomas
title_short Comprehensive Mutation Analysis in Colorectal Flat Adenomas
title_sort comprehensive mutation analysis in colorectal flat adenomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407043/
https://www.ncbi.nlm.nih.gov/pubmed/22848674
http://dx.doi.org/10.1371/journal.pone.0041963
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