Oncogenic PIK3CA mutations in colorectal cancers and polyps

Whitehall, Vicki L. J., Rickman, Celestine, Bond, Catherine E., Ramsnes, Ingunn, Greco, Sonia A., Umapathy, Aarti, McKeone, Diane, Faleiro, Rebecca J., Buttenshaw, Ron L., Worthley, Daniel L., Nayler, Sam, Zhao, Zhen Zhen, Montgomery, Grant W., Mallitt, Kylie-Ann, Jass, Jeremy R., Matsubara, Nagahide, Notohara, Kenji, Ishii, Tatsuhiro and Leggett, Barbara A. (2011) Oncogenic PIK3CA mutations in colorectal cancers and polyps. International Journal of Cancer, 131 4: 813-820. doi:10.1002/ijc.26440

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Author Whitehall, Vicki L. J.
Rickman, Celestine
Bond, Catherine E.
Ramsnes, Ingunn
Greco, Sonia A.
Umapathy, Aarti
McKeone, Diane
Faleiro, Rebecca J.
Buttenshaw, Ron L.
Worthley, Daniel L.
Nayler, Sam
Zhao, Zhen Zhen
Montgomery, Grant W.
Mallitt, Kylie-Ann
Jass, Jeremy R.
Matsubara, Nagahide
Notohara, Kenji
Ishii, Tatsuhiro
Leggett, Barbara A.
Title Oncogenic PIK3CA mutations in colorectal cancers and polyps
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
Publication date 2011-11-19
Sub-type Article (original research)
DOI 10.1002/ijc.26440
Volume 131
Issue 4
Start page 813
End page 820
Total pages 8
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2012
Language eng
Formatted abstract
Oncogenic PIK3CA mutations contribute to colorectal tumorigenesis by activating AKT signaling to decrease apoptosis and increase tumor invasion. A synergistic association of PIK3CA mutation with KRAS mutation has been suggested to increase AKT signaling and resistance to antiepidermal growth factor receptor inhibitor therapy for advanced colorectal cancer, although studies have been conflicting. We sought to clarify this by examining PIK3CA mutation frequency in relation to other key molecular features of defined pathways of tumorigenesis. PIK3CA mutation was assessed by high resolution melt analysis in 829 colorectal cancer samples and 426 colorectal polyps. Mutations were independently correlated with clinicopathological features including patient age, sex and tumor location as well as molecular features including microsatellite instability, KRAS and BRAF mutation, MGMT methylation and the CpG Island Methylator Phenotype (CIMP). Mutation of the helical (Exon 9) and catalytic (Exon 20) domain mutation hotspots were also examined independently. Overall, PIK3CA mutation was positively correlated with KRAS mutation (p < 0.001), MGMT methylation (p = 0.007) and CIMP (p < 0.001). Novel, exon-specific associations linked Exon 9 mutations to a subgroup of cancers characterized by KRAS mutation, MGMT methylation and CIMP-Low, whilst Exon 20 mutations were more closely linked to features of serrated pathway tumors including BRAF mutation, microsatellite instability and CIMP-High or Low. PIK3CA mutations were uncommonly, but exclusively, seen in tubulovillous adenomas (4/124, 3.2%) and 1/4 (25.0%) tubulovillous adenomas with a focus of cancer. These data provide insight into the molecular events driving traditional versus serrated pathway tumorigenesis.
Keyword PIK3CA
Microsatellite instability
CpG island methylator phenotype
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes In Press. Article first published online: 19 NOV 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 39 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 16 Dec 2011, 11:50:07 EST by Matthew Lamb on behalf of School of Medicine