E17K substitution in AKT1 in prostate cancer.
BACKGROUND
The phosphatidylinositol 3-kinase (PI3K)-AKT pathway is activated in many cancers. Mutational hotspots in AKT1 and in the regulatory and catalytic subunits of PI3K have been detected in multiple tumour types. In AKT1, the E17K substitution leads to a PI3K-independent activation of AKT1.


METHODS
A mutational profiling of AKT1 and of the mutational hotspots in PIK3CA and PIK3R1 was carried out in samples from primary and recurrent prostate tumours.


RESULTS
We show that, in prostate cancer, AKT1(E17K) had a prevalence of 1.4%. The mutation seemed to be associated with a favourable clinical course but it was not associated with a specific tumour growth pattern. Activating mutations in PIK3CA or PIK3R1 were not found in prostate cancer.


CONCLUSIONS
The E17K substitution in AKT1 is rare in prostate cancer. It seems associated with a favourable clinical outcome but not with a specific histology of the tumour.
Boormans
J L
JL
Department of Urology, Erasmus University Medical Centre, 3000 CA, Rotterdam, The Netherlands. j.boormans@erasmusmc.nl
Korsten
H
H
Ziel-van der Made
A C J
AC
van Leenders
G J L H
GJ
Verhagen
P C M S
PC
Trapman
J
J
D000368:Aged; D004252:DNA Mutational Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
Oncogene. 2005 Nov 14;24(50):7465-74
16288293
Br J Cancer. 2009 Jul 7;101(1):145-8
19491896
Cancer Res. 1998 Jan 15;58(2):204-9
9443392
Science. 1997 Mar 28;275(5308):1943-7
9072974
J Pathol. 2006 Apr;208(5):699-707
16402365
Cancer Res. 2005 Jul 1;65(13):5730-9
15994948
Cancer Genet Cytogenet. 2009 May;191(1):34-7
19389506
Cancer Cell. 2003 Sep;4(3):209-21
14522255
Nature. 2008 Oct 23;455(7216):1061-8
18772890
Cancer Res. 1997 Nov 15;57(22):4997-5000
9371490
BJU Int. 2010 Jun;105(11):1536-40
19912180
Int J Cancer. 2008 Dec 1;123(11):2725-6
18798258
Nat Rev Cancer. 2002 Jul;2(7):489-501
12094235
Cell Cycle. 2009 May 1;8(9):1352-8
19305151
Cell Cycle. 2008 Mar 1;7(5):665-9
18256540
Science. 2007 Dec 14;318(5857):1744-8
18079394
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4240-5
10200246
Science. 2008 Sep 26;321(5897):1807-12
18772396
BMC Res Notes. 2008 May 16;1:14
18611285
Clin Cancer Res. 2005 Apr 15;11(8):2875-8
15837735
Cancer Cell. 2007 Aug;12(2):104-7
17692802
Science. 2004 Apr 23;304(5670):554
15016963
Oncogene. 2008 Sep 18;27(42):5648-50
18504432
Cancer Res. 1998 Jul 1;58(13):2720-3
9661880
Nature. 2007 Jul 26;448(7152):439-44
17611497
Br J Cancer. 2008 Oct 21;99(8):1265-8
18813315
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5246-50
9560261