|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
We analyzed tumor growth in mice that expressed the oncogenic form of KRAS (KRAS(G12D)) in pancreatic precursor cells, as well as sst2+/- and sst2-/-, and in crossed KRAS(G12D);sst2+/- and KRAS(G12D);sst2-/- mice.
|
25683115 |
2015 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Furthermore, isoform-selective inhibitors showed a similar pattern of the isoform dependence in established Kras(G12D)/PTEN-deficient tumors.
|
24737887 |
2014 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Most genes from this signature are also upregulated in poorly differentiated tumors developing in Pten(thyr-/-),Kras(G12D) mice.
|
23509868 |
2013 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Treatment of Kras(G12D) mice with either of two distinct small molecule Pak inhibitors (PF3758309 and FRAX597) caused tumor regression and loss of Erk and Akt activity.
|
22983922 |
2012 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Moreover, we show that KRAS(G12D)- and BRAF(V600E)-induced tumor formation in an orthotopic model requires IGF1R.
|
22871572 |
2012 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
Finally, m-CT imaging in live Kras(G12D-LSL) mice showed reduction of tumor burdens in PD-0325901-treated animals at sub-MTD dose.
|
22684718 |
2012 |
|
rs752021744
|
|
Neoplasms
|
|
0.070 |
GeneticVariation
|
BEFREE |
In LSL-K-ras(G12D/+)Pten(loxP/loxP) mice with established intraperitoneal tumor disease, oral administration of NVP-BEZ235 decreased pAkt, p4E-BP1 and Ki67 in tumor tissue, and resulted in significantly longer survival compared to control animals (P < 0.05).
|
21372221 |
2011 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
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 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
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 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
GeneticVariation
|
BEFREE |
The E545K mutation promoted proliferation, migration and invasion of GBC cells in vitro and tumor proliferation in vivo.
|
27317099 |
2016 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
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 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
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 |
|
rs752742313
|
|
Neoplasms
|
|
0.060 |
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 |
|
rs752742313
|
|
Malignant neoplasm of breast
|
|
0.030 |
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 |
|
rs752742313
|
|
Malignant neoplasm of breast
|
|
0.030 |
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 |
|
rs752742313
|
|
Malignant neoplasm of breast
|
|
0.030 |
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 |
|
rs361072
|
|
Obesity
|
|
0.020 |
GeneticVariation
|
BEFREE |
No association with HOMA-IR or type 2 diabetes (odds ratio 1.07, P = 0.5) was identified, and obesity did not interact with rs361072 on these traits.
|
20107106 |
2010 |
|
rs361072
|
|
Diabetes Mellitus, Non-Insulin-Dependent
|
|
0.020 |
GeneticVariation
|
BEFREE |
No association with HOMA-IR or type 2 diabetes (odds ratio 1.07, P = 0.5) was identified, and obesity did not interact with rs361072 on these traits.
|
20107106 |
2010 |
|
rs361072
|
|
Diabetes Mellitus, Non-Insulin-Dependent
|
|
0.020 |
GeneticVariation
|
BEFREE |
In obese and non-obese adults, the cis-regulatory rs361072 promoter variant of PIK3CB is associated with insulin resistance not with type 2 diabetes.
|
19097921 |
2009 |
|
rs361072
|
|
Obesity
|
|
0.020 |
GeneticVariation
|
BEFREE |
GATA-binding and functional effects of rs361072 were explored in transfected cell lines and in lymphocytes from obese children.
|
17977952 |
2008 |
|
rs752021744
|
|
Secondary Neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
GTPase-impairing somatic mutations in RAS genes, such as KRAS(G12D), are among the most common oncogenic events in metastatic cancer.
|
26549032 |
2016 |
|
rs752021744
|
|
Neoplasm Metastasis
|
|
0.020 |
GeneticVariation
|
BEFREE |
GTPase-impairing somatic mutations in RAS genes, such as KRAS(G12D), are among the most common oncogenic events in metastatic cancer.
|
26549032 |
2016 |
|
rs752021744
|
|
Carcinogenesis
|
|
0.020 |
GeneticVariation
|
BEFREE |
Administration of a CXCL16-neutralizing antibody to KRAS(G12D) mice reduced activation of PI3K signaling to AKT and NF-κB, blocking carcinogenesis.
|
25683115 |
2015 |
|
rs752021744
|
|
Primary malignant neoplasm
|
|
0.020 |
GeneticVariation
|
BEFREE |
Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches.
|
25877892 |
2015 |
|
rs752021744
|
|
Malignant Neoplasms
|
|
0.020 |
GeneticVariation
|
BEFREE |
Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches.
|
25877892 |
2015 |