Multiple APC mutations in sporadic flat colorectal adenomas

Wyk, René van; Slezak, P; Kotze, Maritha J.; Jaramillo, Edgar; Koizumi, Koichi; Grobbelaar, Johanna J.

doi:10.1038/sj.ejhg.5200386

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…27 Mutational analysis using the protein truncation test has revealed multiple APC mutations in flat adenomas and aberrant expression of key cell cycle components in a significant subset of these adenomas. 28,29 Our findings not only support previous observations [15][16][17] that activated PPAR-g enhanced colonic carcinogenesis in genetically altered mice but also show for the first time that normal mice not exposed to a carcinogen or gene targeting respond to TGZ administration with formation of tumors in the large intestine, clearly indicating that preexisting mutational events are not necessary for in vivo cancer-inducing action of activated PPAR-g.…”

Section: Table II -Multiplicity and Volume Of Intestinal Tumors In Nosupporting

confidence: 80%

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc^{1638 N/+}Mlh1^+/− double mutant mice

Yang

Fan

Lamprecht

et al. 2005

Intl Journal of Cancer

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The role of the nuclear peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) in colon tumorigenesis remains controversial. Notwithstanding evidence that PPAR‐γ ligands impede murine colorectal carcinogenesis, PPAR‐γ agonists have been shown to enhance in vivo tumor formation in mouse models of human colon cancer. Our study was designed to determine whether troglitazone (TGZ) induces colonic tumor formation in normal C57BL/6J mice and enhances colorectal carcinogenesis in double mutant Apc1638N/+Mlh1+/− mice fed a standard AIN‐76A diet. We report herein that not only does TGZ enhance carcinogenesis in the large intestine of mutant mice predisposed to intestinal carcinogenesis but TGZ also induces colonic tumors in normal mice without gene targeting or carcinogen administration. This observation indicates that preexisting mutational events are not necessary for induction of colonic tumors by activated PPAR‐γ in vivo. © 2005 Wiley‐Liss, Inc.

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Section: Table II -Multiplicity and Volume Of Intestinal Tumors In Nosupporting

confidence: 80%

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc^{1638 N/+}Mlh1^+/− double mutant mice

Yang

Fan

Lamprecht

et al. 2005

Intl Journal of Cancer

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“…Double mutations are not unique and are frequently reported in the literature especially in familial adenomatous polyposis (FAP) patients [48], [49].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Mutation Analysis in Colorectal Flat Adenomas

et al. 2012

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BackgroundFlat 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.MethodsA 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.ConclusionThe 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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Mutation analysis of APC gene in gastric cancer with microsatellite instability

Fang

Luo²,

Yang³

et al. 2002

WJG

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Multiple APC mutations in sporadic flat colorectal adenomas

Cited by 3 publications

References 13 publications

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc^{1638 N/+}Mlh1^+/− double mutant mice

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc^{1638 N/+}Mlh1^+/− double mutant mice

Comprehensive Mutation Analysis in Colorectal Flat Adenomas

Mutation analysis of APC gene in gastric cancer with microsatellite instability

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Multiple APC mutations in sporadic flat colorectal adenomas

Cited by 3 publications

References 13 publications

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638 N/+Mlh1+/− double mutant mice

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638 N/+Mlh1+/− double mutant mice

Comprehensive Mutation Analysis in Colorectal Flat Adenomas

Mutation analysis of APC gene in gastric cancer with microsatellite instability

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Product

Resources

About

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc^{1638 N/+}Mlh1^+/− double mutant mice

Peroxisome proliferator‐activated receptor γ agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc^{1638 N/+}Mlh1^+/− double mutant mice