PIK3CA Activating Mutation in Colorectal Carcinoma: Associations with Molecular Features and Survival

Rosty, Christophe, Young, Joanne P., Walsh, Michael D., Clendenning, Mark, Sanderson, Kristy, Walters, Rhiannon J., Parry, Susan, Jenkins, Mark A., Win, Aung Ko, Southey, Melissa C., Hopper, John L., Giles, Graham G., Williamson, Elizabeth J., English, Dallas R. and Buchanan, Daniel D. (2013) PIK3CA Activating Mutation in Colorectal Carcinoma: Associations with Molecular Features and Survival. PloS One, 8 6: e65479.1-e65479.8. doi:10.1371/journal.pone.0065479


Author Rosty, Christophe
Young, Joanne P.
Walsh, Michael D.
Clendenning, Mark
Sanderson, Kristy
Walters, Rhiannon J.
Parry, Susan
Jenkins, Mark A.
Win, Aung Ko
Southey, Melissa C.
Hopper, John L.
Giles, Graham G.
Williamson, Elizabeth J.
English, Dallas R.
Buchanan, Daniel D.
Title PIK3CA Activating Mutation in Colorectal Carcinoma: Associations with Molecular Features and Survival
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-06
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0065479
Open Access Status DOI
Volume 8
Issue 6
Start page e65479.1
End page e65479.8
Total pages 9
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
Mutations in PIK3CA are present in 10 to 15% of colorectal carcinomas. We aimed to examine how PIK3CA mutations relate to other molecular alterations in colorectal carcinoma, to pathologic phenotype and survival. PIK3CA mutation testing was carried out using direct sequencing on 757 incident tumors from the Melbourne Collaborative Cohort Study. The status of O-6-methylguanine-DNA methyltransferase (MGMT) was assessed using both immunohistochemistry and methyLight techniques. Microsatellite instability, CpG island phenotype (CIMP), KRAS and BRAF V600E mutation status, and pathology review features were derived from previous reports. PIK3CA mutation was observed in 105 of 757 (14%) of carcinomas, characterized by location in the proximal colon (54% vs. 34%; P<0.001) and an increased frequency of KRAS mutation (48% vs. 25%; P<0.001). High-levels of CIMP were more frequently found in PIK3CA-mutated tumors compared with PIK3CA wild-type tumors (22% vs. 11%; P = 0.004). There was no difference in the prevalence of BRAF V600E mutation between these two tumor groups. PIK3CA-mutated tumors were associated with loss of MGMT expression (35% vs. 20%; P = 0.001) and the presence of tumor mucinous differentiation (54% vs. 32%; P<0.001). In patients with wild-type BRAF tumors, PIK3CA mutation was associated with poor survival (HR 1.51 95% CI 1.04-2.19, P = 0.03). In summary, PIK3CA-mutated colorectal carcinomas are more likely to develop in the proximal colon, to demonstrate high levels of CIMP, KRAS mutation and loss of MGMT expression. PIK3CA mutation also contributes to significantly decreased survival for patients with wild-type BRAF tumors.
Keyword Receptor Inhibitor Cetuximab
Island Methylator Phenotype
Braf V600E Mutation
Colon Cancer Cells
Poor Survival
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 42 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 11 Aug 2013, 00:09:37 EST by System User on behalf of School of Medicine