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| PMID |
|
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| TITLE |
|
| Oncogenic PIK3CA mutations in colorectal cancers and polyps. |
|
| ABSTRACT |
|
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|
| 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. |
| Copyright © 2011 UICC. |
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| DATE PUBLISHED |
|
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| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| accepted |
2011/08/31 |
| received |
2011/11/17 |
| aheadofprint |
2011/11/19 |
| entrez |
2011/09/21 06:00 |
| pubmed |
2011/09/21 06:00 |
| medline |
2012/09/01 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Whitehall VL |
|
Whitehall |
Vicki L J |
VL |
|
Queensland Institute of Medical Research, Brisbane, Australia. Whitehall@qimr.edu.au |
| Rickman C |
|
Rickman |
Celestine |
C |
|
|
| Bond CE |
|
Bond |
Catherine E |
CE |
|
|
| Ramsnes I |
|
Ramsnes |
Ingunn |
I |
|
|
| Greco SA |
|
Greco |
Sonia A |
SA |
|
|
| Umapathy A |
|
Umapathy |
Aarti |
A |
|
|
| McKeone D |
|
McKeone |
Diane |
D |
|
|
| Faleiro RJ |
|
Faleiro |
Rebecca J |
RJ |
|
|
| Buttenshaw RL |
|
Buttenshaw |
Ron L |
RL |
|
|
| Worthley DL |
|
Worthley |
Daniel L |
DL |
|
|
| Nayler S |
|
Nayler |
Sam |
S |
|
|
| Zhao ZZ |
|
Zhao |
Zhen Zhen |
ZZ |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Mallitt KA |
|
Mallitt |
Kylie-Ann |
KA |
|
|
| Jass JR |
|
Jass |
Jeremy R |
JR |
|
|
| Matsubara N |
|
Matsubara |
Nagahide |
N |
|
|
| Notohara K |
|
Notohara |
Kenji |
K |
|
|
| Ishii T |
|
Ishii |
Tatsuhiro |
T |
|
|
| Leggett BA |
|
Leggett |
Barbara A |
BA |
|
|
|
| INVESTIGATORS |
|
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| JOURNAL |
|
| VOLUME: 131 |
| ISSUE: 4 |
| TITLE: International journal of cancer |
| ISOABBREVIATION: Int. J. Cancer |
| YEAR: 2012 |
| MONTH: Aug |
| DAY: 15 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1097-0215 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Int J Cancer |
| COUNTRY: United States |
| ISSNLINKING: 0020-7136 |
| NLMUNIQUEID: 0042124 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
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| GRANTS |
|
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| GENERAL NOTE |
|
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| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Aged |
|
| Base Sequence |
|
| Cohort Studies |
|
| Colonic Polyps |
genetics |
| Colorectal Neoplasms |
genetics |
| DNA Primers |
genetics |
| Female |
genetics |
| Humans |
genetics |
| Male |
genetics |
| Middle Aged |
genetics |
| Oncogenes |
genetics |
| Phosphatidylinositol 3-Kinases |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
DNA Primers |
| EC 2.7.1.- |
Phosphatidylinositol 3-Kinases |
| EC 2.7.1.137 |
PIK3CA protein, human |
|
| OTHER ID's |
|
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|
