Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer

The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k‐ras oncogene and of the p53 oncosuppressor gene during the adenoma–carcinoma sequence by inv...

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Main Authors:	Giaretti, Walter, Macciocu, Barbara, Geido, Elio, Hermsen, Mario, Postma, Cindy, Baak, Jan, Williams, Richard, Meijer, Gerrit
Format:	Online
Language:	English
Published:	IOS Press 2000
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615987/

id	pubmed-4615987
recordtype	oai_dc
spelling	pubmed-46159872016-01-12 Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer Giaretti, Walter Macciocu, Barbara Geido, Elio Hermsen, Mario Postma, Cindy Baak, Jan Williams, Richard Meijer, Gerrit Other The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k‐ras oncogene and of the p53 oncosuppressor gene during the adenoma–carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer. An intratumor comparative analysis was obtained among the adenomatous and carcinomatous component pairs. Additionally, we have analyzed 17 adenomas having cancer in the near vicinity. The adenomatous components of the adenomas containing early cancer and the adenomas having cancer in the near vicinity had comparable frequencies for k‐ras mutations (28 and 47%) but different for p53 mutations (52 and 7%, p‐value = 0.01). Interestingly, the adenomatous and carcinomatous components of the adenomas containing early cancer were rarely heterogeneous for the k‐ras mutational status (only in 13% of the cases) but were characterized by heterogeneity of the p53 status in 59% of the cases (p‐value < 0.01). In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p-value = 0.01). Intratumor homogeneity of k‐ras status during the human colorectal adenoma–carcinoma sequence suggests that the role of k‐ras is more related to tumor initiation than to tumor progression. On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression. IOS Press 2000 2000-01-01 /pmc/articles/PMC4615987/ /pubmed/11310641 http://dx.doi.org/10.1155/2000/747524 Text en Copyright © 2000 Hindawi Publishing Corporation.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Giaretti, Walter Macciocu, Barbara Geido, Elio Hermsen, Mario Postma, Cindy Baak, Jan Williams, Richard Meijer, Gerrit
spellingShingle	Giaretti, Walter Macciocu, Barbara Geido, Elio Hermsen, Mario Postma, Cindy Baak, Jan Williams, Richard Meijer, Gerrit Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
author_facet	Giaretti, Walter Macciocu, Barbara Geido, Elio Hermsen, Mario Postma, Cindy Baak, Jan Williams, Richard Meijer, Gerrit
author_sort	Giaretti, Walter
title	Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
title_short	Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
title_full	Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
title_fullStr	Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
title_full_unstemmed	Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer
title_sort	intratumor heterogeneity of k-ras and p53 mutations among human colorectal adenomas containing early cancer
description	The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k‐ras oncogene and of the p53 oncosuppressor gene during the adenoma–carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer. An intratumor comparative analysis was obtained among the adenomatous and carcinomatous component pairs. Additionally, we have analyzed 17 adenomas having cancer in the near vicinity. The adenomatous components of the adenomas containing early cancer and the adenomas having cancer in the near vicinity had comparable frequencies for k‐ras mutations (28 and 47%) but different for p53 mutations (52 and 7%, p‐value = 0.01). Interestingly, the adenomatous and carcinomatous components of the adenomas containing early cancer were rarely heterogeneous for the k‐ras mutational status (only in 13% of the cases) but were characterized by heterogeneity of the p53 status in 59% of the cases (p‐value < 0.01). In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p-value = 0.01). Intratumor homogeneity of k‐ras status during the human colorectal adenoma–carcinoma sequence suggests that the role of k‐ras is more related to tumor initiation than to tumor progression. On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.
publisher	IOS Press
publishDate	2000
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615987/
_version_	1613491249947344896

Intratumor Heterogeneity of K-Ras and p53 Mutations among Human Colorectal Adenomas Containing Early Cancer

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