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rs104886003
|
|
Malignant neoplasm of breast
|
|
0.760 |
GeneticVariation
|
BEFREE |
Using a variety of physiologically relevant model systems with defined natural or knock-in PIK3CA mutations and/or PI3K hyperactivation, we show that PIK3CA-E545K mutations (found in ∼20% of PIK3CA-mutant breast cancers), but not PIK3CA-H1047R mutations (found in 55% of PIK3CA-mutant breast cancers), preferentially activate AKT1.
|
27197157 |
2016 |
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rs104886003
|
|
Malignant neoplasm of breast
|
|
0.760 |
GeneticVariation
|
BEFREE |
This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common activating mutations in human breast cancer (BC), and the efficacy of neoadjuvant chemotherapy (NCT).Using a novel liquid chip technology,PIK3CA DNA somatic mutations and HER2, PTEN, EGFR mRNA expression profiles were analyzed in formalin fixed paraffin embedded samples of 93 BC patients treated with epirubicin plus docetaxel NCT.PIK3CA mutations were found in 30 patients (32.3%), in which the point mutations of E542K, E545K, H1047L and H1047R were 4.3, 9.7, 4.3 and 14.0%respectively.
|
25027743 |
2014 |
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rs104886003
|
|
Malignant neoplasm of breast
|
|
0.760 |
GeneticVariation
|
BEFREE |
In this study, we directly compared PIK3CA hotspot mutations (E545K, H1047R) in EpCAM-positive CTCs and paired plasma-ctDNA in breast cancer (BrCa).
|
31254443 |
2019 |
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rs104886003
|
|
Malignant neoplasm of breast
|
|
0.760 |
GeneticVariation
|
BEFREE |
PIK3CA mutations are seemingly the most common driver mutations in breast cancer with H1047R and E545K being the most common of these, accounting together for around 60% of all PIK3CA mutations and have promising therapeutic implications.
|
29523855 |
2018 |
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rs104886003
|
|
Malignant neoplasm of breast
|
|
0.760 |
GeneticVariation
|
BEFREE |
Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry.
|
28123607 |
2017 |
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rs104886003
|
|
Malignant neoplasm of breast
|
|
0.760 |
GeneticVariation
|
BEFREE |
We further validated the approach in breast cancer cells with mutational activation of PIK3CA, where tandem mass spectrometry detected and quantitatively measured the abundance of a helical domain mutant (E545K) of PIK3CA connected to PI3K activation.
|
21775521 |
2011 |
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rs104886003
|
|
Liver carcinoma
|
|
0.720 |
GeneticVariation
|
BEFREE |
PIK3CA missense mutations were found in one of 11 intrahepatic CCA (E545K, 9%), one of 23 gallbladder carcinomas (E542K, 4%), and one of 50 hepatocellular carcinomas (H1047R, 2%).
|
18181165 |
2008 |
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rs104886003
|
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Gallbladder Carcinoma
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|
0.720 |
GeneticVariation
|
BEFREE |
Mutations in exons 9 (E542K, E545G, E545K) and 20 (H1047L and H1047R) of PI3K were determined by direct sequencing in 130 cases of GBC.
|
26947513 |
2016 |
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rs104886003
|
|
Gallbladder Carcinoma
|
|
0.720 |
GeneticVariation
|
BEFREE |
The E545K mutation promoted GBC progression through enhanced binding to EGFR and activating downstream akt activity.
|
27317099 |
2016 |
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rs104886003
|
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Liver carcinoma
|
|
0.720 |
GeneticVariation
|
BEFREE |
Similarly, in human HCC cell lines, silencing of SGK3 reduced PIK3CA(E545K</span>) -but not PIK3CA(H1047R)- induced accelerated tumor cell proliferation.
|
30975125 |
2019 |
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rs104886003
|
|
ovarian neoplasm
|
|
0.710 |
GeneticVariation
|
BEFREE |
We also found that an activating (E545K) Pik3ca mutation, unlike Pten inactivation or Pik3ca H1047R mutation, cannot cooperate with Arid1a loss to promote ovarian cancer development in the mouse.
|
26279473 |
2016 |
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rs104886003
|
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Esophageal carcinoma
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|
0.710 |
GeneticVariation
|
BEFREE |
PI3K inhibitor (LY294002) inhibited the growth of an esophageal cancer cell line with a PIK3CA mutation (E545K) in vitro.
|
18262558 |
2008 |
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rs104886003
|
|
Mammary Neoplasms
|
|
0.710 |
GeneticVariation
|
BEFREE |
In addition, the combined treatment of DSF and LY294002 significantly inhibited the growth of the breast tumor xenograft in nude mice induced by MDA-MB-231 cells expressing mutant PIK3CA-H1047R and PIK3CA-E545K, whereas neither DSF nor LY294002 alone could significantly retard tumor growth.
|
20424113 |
2010 |
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rs104886003
|
|
Uterine Cervical Neoplasm
|
|
0.710 |
GeneticVariation
|
BEFREE |
Our cervical tumor mutational landscape shows that most mutations are found in PIK3CA (E545K, E542K) and KRAS (G12D, G13D) and others in FBXW7 (R465C, R505G, R479Q).
|
26155992 |
2015 |
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rs104886003
|
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Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC.
|
25839328 |
2015 |
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rs104886003
|
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Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Similarly, in human HCC cell lines, silencing of SGK3 reduced PIK3CA(E545K) -but not PIK3CA(H1047R)- induced accelerated tumor cell proliferation.
|
30975125 |
2019 |
|
rs104886003
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
As a proof of the concept, we present the case of a metastatic patient with a PIK3CA wild-type primary tumor in which the PIK3CA E545K mutation was identified in both the circulating-free DNA obtained from a peripheral blood sample and in the formalin-fixed, paraffin-embedded liver metastasis.
|
26001593 |
2015 |
|
rs104886003
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
PIK3CA mutations were detected in 25% of tumors and 26% of cell lines with a significant excess of helical domain mutations (E542K and E545K).
|
19789314 |
2009 |
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rs104886003
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Disruption of the IRS1-p110α E545K interaction destabilizes the p110α protein, reduces AKT phosphorylation, and slows xenograft tumor growth of a cancer cell line expressing p110α E545K.
|
23643389 |
2013 |
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rs104886003
|
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Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
The E545K mutation promoted proliferation, migration and invasion of GBC cells in vitro and tumor proliferation in vivo.
|
27317099 |
2016 |
|
rs104886003
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Sequencing of tumors identified seven PIK3CA exon 20 mutations (H1047R) and three exon 9 mutations (E545K).
|
24504125 |
2014 |
|
rs104886003
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
PIK3CA mutations were predominantly occurred in p.E545K and p.E542K on exon 9 in moderately to poorly differentiated tumors.
|
30266251 |
2019 |
|
rs104886003
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry.
|
28123607 |
2017 |
|
rs104886003
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
KRAS mutations were detected in 4 (3%) of 117 tumors (3× G12D and 1 G12V mutation).One tumor had a PIK3CA E545K mutation.
|
23158210 |
2013 |
|
rs104886003
|
|
Breast Carcinoma
|
|
0.050 |
GeneticVariation
|
BEFREE |
Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overexpressing breast cancer patients treated with radical local therapy and trastuzumab in adjuvant setting were used for the assessment of: (1) PIK3CA gene mutations (p.H1047R and p.E545K) by qPCR, and (2) expression of Ki-67, EGFR, MUC4, HER3 and PTEN by immunohistochemistry.
|
28123607 |
2017 |