|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
To elucidate mechanisms of resistance to PI3K-targeted therapy, we constructed a mouse model of breast cancer conditionally expressing human PIK3CA(H1047R).
|
21822287 |
2011 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The hotspot mutation H1047R in the oncogenic PIK3CA gene is frequently detected in breast cancer and enhances the enzymatic activity of PI3K to activate AKT/mTOR signaling cascade.
|
30671946 |
2019 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The aim of this study was to analyze the efficacy of PI3K/mTOR blockade in breast cancer brain metastases models.<b>Experimental Design:</b> The efficacy of GDC-0084 was evaluated in <i>PIK3CA</i>-mutant and <i>PIK3CA</i> wild-type breast cancer cell lines and the isogenic pairs of <i>PIK3CA</i> wild-type and mutant (H1047R/+) MCF10A cells <i>in vitro</i>.
|
30796030 |
2019 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
In trastuzumab-resistant BT474 H1047R breast cancer xenografts, NVP-BEZ235 inhibited PI3K signaling and had potent antitumor activity.
|
18829560 |
2008 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial cells induces tumorigenesis, implying that PIK3CA mutation is an early event in breast cancer.
|
22315990 |
2012 |
|
Breast Carcinoma
|
|
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 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells.
|
27108388 |
2016 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
This derivative showed low micromolar cytotoxic potency in all BrCa cell lines, a mild inhibition of the PI3Kα wild type and H1047R mutated enzyme and excellent pharmacokinetic parameters following oral and intraperitoneal administration at the designed dose of 10 mg/kg, with absence of in vivo phenotypic toxicity.
|
28006668 |
2017 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Gene set enrichment analysis reveals a highly significant concordance of the genes differentially expressed in MCF-10A-H1047R cells and the established protein and RNA signatures of basal breast cancer.
|
25583473 |
2015 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
Using in situ genetic lineage tracing and limiting dilution transplantation, we have unravelled the potential of PIK3CA(H1047R), one of the most frequent mutations occurring in human breast cancer, to induce multipotency during tumorigenesis in the mammary gland.
|
26266975 |
2015 |
|
Breast Carcinoma
|
|
0.100 |
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 |
|
Breast Carcinoma
|
|
0.100 |
GeneticVariation
|
BEFREE |
The incidence of point mutations in PIK3CA, the A3140G substitution in particular, in Singapore breast cancers are among the most frequent reported to date for any gene in breast cancer.
|
16582596 |
2006 |
|
Carcinogenesis
|
|
0.060 |
GeneticVariation
|
BEFREE |
Structural Perturbations due to Mutation (H1047R) in Phosphoinositide-3-kinase (PI3Kα) and Its Involvement in Oncogenesis: An in Silico Insight.
|
31592171 |
2019 |
|
Carcinogenesis
|
|
0.060 |
GeneticVariation
|
BEFREE |
The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells.
|
27108388 |
2016 |
|
Carcinogenesis
|
|
0.060 |
GeneticVariation
|
BEFREE |
Recent studies by Meyer and colleagues, and Liu and colleagues demonstrate that expression of the H1047R exon 20 mutant of PIK3CA in luminal mammary epithelial cells induces tumorigenesis, implying that PIK3CA mutation is an early event in breast cancer.
|
22315990 |
2012 |
|
Carcinogenesis
|
|
0.060 |
GeneticVariation
|
BEFREE |
PIK3CA(H1047R) expression alone failed to promote tumor formation, but dramatically enhanced tumorigenesis initiated by KRAS(G12D).
|
26567140 |
2015 |
|
Carcinogenesis
|
|
0.060 |
GeneticVariation
|
BEFREE |
Using in situ genetic lineage tracing and limiting dilution transplantation, we have unravelled the potential of PIK3CA(H1047R), one of the most frequent mutations occurring in human breast cancer, to induce multipotency during tumorigenesis in the mammary gland.
|
26266975 |
2015 |
|
Carcinogenesis
|
|
0.060 |
GeneticVariation
|
BEFREE |
To better understand the role of mutant PIK3CA in the initiation or progression of tumorigenesis, we generated mice in which a PIK3CA mutation commonly detected in human cancers (the H1047R mutation) could be conditionally knocked into the endogenous Pik3ca locus.
|
22214849 |
2012 |
|
Carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
Somatic mutations of the PIK3CA gene were detected in 10/23 (43%) carcinomas and in all cases the type of mutation was H1047R in the kinase domain.
|
21735444 |
2011 |
|
Carcinoma
|
|
0.020 |
GeneticVariation
|
BEFREE |
RNA sequencing and Sanger sequencing identified PIK3CA (p.E545K/p.H1047R) and/or HRAS (p.Q61R) hotspot mutations in 6 of 8 (75%) apocrine carcinomas.
|
29443014 |
2018 |
|
Carcinoma breast stage IV
|
|
0.010 |
GeneticVariation
|
BEFREE |
Everolimus in hormone receptor-positive metastatic breast cancer: PIK3CA mutation H1047R was a potential efficacy biomarker in a retrospective study.
|
31088410 |
2019 |
|
Carcinoma of bladder
|
|
0.010 |
GeneticVariation
|
BEFREE |
Potential predictive biomarkers for pictilisib were evaluated, and RNA sequencing was performed to explore drug resistance mechanisms.<b>Results:</b> The bladder cancer cell line TCCSUP, which harbors a <i>PIK3CA</i> E545K mutation, was sensitive to pictilisib compared to cell lines with wild-type <i>PIK3CA</i> Pictilisib exhibited stronger antitumor activity in bladder cancer PDX models with <i>PI3KCA</i> H1047R mutation or amplification than the control PDX model.
|
28808038 |
2017 |
|
Carcinoma of lung
|
|
0.010 |
GeneticVariation
|
BEFREE |
We further observed that oncogenic cooperation between KRAS(G12D) and PIK3CA(H1047R) was accompanied by PI3Kα-mediated regulation of c-MYC, GSK3β, p27(KIP1), survivin, and components of the RB pathway, resulting in accelerated cell division of human or mouse lung cancer-derived cell lines.
|
26567140 |
2015 |
|
Carcinoma, Ovarian Epithelial
|
|
0.010 |
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 |
|
Cerebellar Granule Cell Hypertrophy and Megalencephaly
|
|
0.700 |
CausalMutation
|
CLINVAR |
|
|
|