IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1167/iovs.09-3617 on May 6, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:5054-5056.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.09-3617
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
iovs.09-3617v1
50/11/5054    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Cohen, Y.
Right arrow Articles by Goldenberg-Cohen, N.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cohen, Y.
Right arrow Articles by Goldenberg-Cohen, N.

PI3K/Akt Pathway Mutations in Retinoblastoma

Yoram Cohen,1 Efrat Merhavi-Shoham,2 Bat Chen R. Avraham-Lubin,2,3 Michael Savetsky,2 Shahar Frenkel,4 Jacob Pe'er,4 and Nitza Goldenberg-Cohen2,3,5

From the 1Department of Gynecology, Sheba Medical Center, Tel Hashomer, Israel; 2The Krieger Eye Research Laboratory, Felsenstein Medical Research Center, Petah Tiqwa, Israel; the 4Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; the 5Department of Ophthalmology, Pediatric Unit, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel; and the 3Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Corresponding author: N. Goldenberg-Cohen, Department of Ophthalmology, Pediatric Unit, Schneider Children's Medical Center of Israel, Petah Tiqwa 49100, Israel; ncohen1{at}gmail.com.

Purpose. Many malignancies are known to be associated with abnormal activation of the PI3K-AKT pathway. Recently, a somatic mutation in the AKT1 gene (E17K) was identified in a small proportion of human tumors. This mutation activated AKT1 by means of abnormal membrane recruitment and stimulated downstream signaling. This study was designed to analyze AKT1 mutations in retinoblastoma and gain insights into the role PI3K-AKT pathway plays in the development of this tumor.

Methods. Twenty-four samples of retinoblastoma from children were analyzed for mutations in the AKT1, PTEN and K-RAS genes, using a chip-based matrix-assisted laser desorption-time-of-flight (MALDI-TOF) mass spectrometer. Mutations in the PIK3CA gene were analyzed in 16 retinoblastoma samples using direct sequencing.

Results. These results show that the mutation E17K/AKT1 was not detected in the 24 samples of retinoblastoma analyzed. K-RAS mutations were identified in two samples. There were no mutations in any of the other genes analyzed by a mass array system. On direct sequencing of 16 samples for the PIK3CA gene, one sample showed gain of function mutation in exon 9. In another sample, a genetic polymorphism of unknown significance (rs17849079) was detected in exon 20.

Conclusions. Although the PI3K-AKT pathway is known to be dysregulated in retinoblastoma, the low frequency of oncogenic mutations in the AKT1, PIK3CA, and PTEN genes, suggests a different activating mechanism.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the Association for Research in Vision and Ophthalmology