PMID- 19638206
OWN - NLM
STAT- MEDLINE
DCOM- 20091020
LR  - 20211020
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 8
DP  - 2009 Jul 28
TI  - PIK3CA alterations in Middle Eastern ovarian cancers.
PG  - 51
LID - 10.1186/1476-4598-8-51 [doi]
AB  - BACKGROUND: PI3K/AKTsignaling pathway plays an important role in cell growth, 
      proliferation, and tumorgenesis of various malignancies. This signaling pathway 
      has been shown to be frequently altered in several human cancers including 
      ovarian cancers. However the role of this oncogenic signaling pathway has not 
      been explored in the Middle Eastern epithelial ovarian cancer (EOC). Therefore, 
      we investigated PI3K/AKT genetic alterations such as PIK3CA amplification, PIK3CA 
      mutation, PTEN protein loss and their relationships with various 
      clinicopathological characteristics in 156 EOCs. RESULTS: Fluorescence in situ 
      hybridization (FISH) technique and DNA sequencing were used to analyze PIK3CA 
      amplification and mutation respectively. Expression of PIK3CA protein expression 
      (p110 alpha), PTEN, p-AKT and Ki-67 was analyzed by immunohistochemistry. PIK3CA 
      amplification was seen in 54 of 152 (35.5%) EOC cases analyzed; PIK3CA gene 
      mutations in 6/153 EOC (3.9%); KRAS mutations in 3/154 EOC (1.9%), BRAF mutations 
      in 3/156 EOC (1.9%), p53 mutation in 50/154 EOC (32.5%), and loss of PTEN protein 
      expression in 33/144 EOC (22.9%). p110 alpha overexpression was associated with 
      increased phosphorylation of AKT-Ser 473 and with the proliferation marker Ki-67. 
      CONCLUSION: Our data showed mutual exclusivity between the molecular event of 
      PIK3CA amplification and mutations in PIK3CA, KRAS, BRAF genes, which suggests 
      that each of these alterations may individually be sufficient to drive ovarian 
      tumor pathogenesis independently. High prevalence of genetic alterations in 
      PI3K/AKT pathway in a Middle Eastern ovarian carcinoma provides genetic evidence 
      supporting the notion that dysregulated PI3K/AKT pathways play an important role 
      in the pathogenesis of ovarian cancers.
FAU - Abubaker, Jehad
AU  - Abubaker J
AD  - Department of Human Cancer Genomic Research, Research Center, King Faisal 
      Specialist Hospital and Research Center, Riyadh, Saudi Arabia. 
      jabubakr@kfshrc.edu.sa
FAU - Bavi, Prashant
AU  - Bavi P
FAU - Al-Haqawi, Wael
AU  - Al-Haqawi W
FAU - Jehan, Zeenath
AU  - Jehan Z
FAU - Munkarah, Adnan
AU  - Munkarah A
FAU - Uddin, Shahab
AU  - Uddin S
FAU - Al-Kuraya, Khawla S
AU  - Al-Kuraya KS
LA  - eng
PT  - Journal Article
DEP - 20090728
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (PIK3CA protein, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/biosynthesis/genetics
MH  - Class I Phosphatidylinositol 3-Kinases
MH  - DNA Mutational Analysis
MH  - Extracellular Signal-Regulated MAP Kinases/genetics
MH  - Female
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Gene Silencing
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Ovarian Neoplasms/*enzymology/*genetics
MH  - PTEN Phosphohydrolase/genetics
MH  - Phosphatidylinositol 3-Kinases/biosynthesis/*genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Saudi Arabia
MH  - Signal Transduction
MH  - Tumor Suppressor Protein p53/genetics
MH  - ras Proteins/genetics
PMC - PMC2724395
EDAT- 2009/07/30 09:00
MHDA- 2009/10/21 06:00
PMCR- 2009/07/28
CRDT- 2009/07/30 09:00
PHST- 2009/06/10 00:00 [received]
PHST- 2009/07/28 00:00 [accepted]
PHST- 2009/07/30 09:00 [entrez]
PHST- 2009/07/30 09:00 [pubmed]
PHST- 2009/10/21 06:00 [medline]
PHST- 2009/07/28 00:00 [pmc-release]
AID - 1476-4598-8-51 [pii]
AID - 10.1186/1476-4598-8-51 [doi]
PST - epublish
SO  - Mol Cancer. 2009 Jul 28;8:51. doi: 10.1186/1476-4598-8-51.