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BIOMARKER:

PIK3R1 mutation

i
Other names: PIK3R1, Phosphoinositide-3-Kinase Regulatory Subunit 1, Phosphatidylinositol 3-Kinase 85 KDa Regulatory Subunit Alpha, Phosphoinositide-3-Kinase, Regulatory Subunit 1 (Alpha), Phosphatidylinositol 3-Kinase Regulatory Subunit Alpha, Phosphoinositide-3-Kinase Regulatory Subunit Alpha, PtdIns-3-Kinase Regulatory Subunit Alpha, PI3K Regulatory Subunit Alpha, PI3-Kinase Subunit P85-Alpha, GRB1, Phosphatidylinositol 3-Kinase, Regulatory Subunit, Polypeptide 1 (P85 Alpha), Phosphatidylinositol 3-Kinase
Entrez ID:
Related biomarkers:
1m
Clinicopathological analysis of rosette-forming glioneuronal tumors. (PubMed, Diagn Pathol)
RGNT is a comparatively rare mixed glioneuronal tumor that occurs in the midline structures. Its morphology shows certain overlaps with other low-grade neuroepithelial tumors. Identifying the rosettes around the neuropil is critical for morphological diagnosis, and the molecular identification of FGFR1 mutations accompanied by PIK3R1 mutations can facilitate diagnosis.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • GFAP (Glial Fibrillary Acidic Protein) • OLIG2 (Oligodendrocyte Transcription Factor 2)
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FGFR1 mutation • PIK3R1 mutation
1m
Tumor Microenvironment and Genomic Profiling of Squamous Cell Carcinomas of the Breast (USCAP 2024)
About half of the breast SCCs exhibited high sTILs and positive PD-L1 expression, which indicated the potential opportunity for immunotherapy. Genomic profile revealed clinically meaningful alterations that might guide targeted treatment decisions in SCC patients.
Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • TERT (Telomerase Reverse Transcriptase) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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PD-L1 expression • TP53 mutation • TMB-H • PIK3CA mutation • PTEN deletion • PTEN mutation • PD-L1 negative • TERT mutation • PIK3CA mutation + PTEN mutation • PIK3R1 mutation • TERT promoter mutation
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PD-L1 IHC 22C3 pharmDx
2ms
Phase 2 Study of PI3K Inhibitor Copanlisib in Combination With Fulvestrant in Selected ER+ and/or PR+ Cancers With PI3K (PIK3CA, PIK3R1) and/or PTEN Alterations (clinicaltrials.gov)
P2, N=7, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2026 --> Aug 2024 | Trial primary completion date: Oct 2026 --> Aug 2024
Trial completion date • Trial primary completion date • Combination therapy
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ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PI3K (Phosphoinositide 3-kinases)
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ER positive • PIK3CA mutation • PTEN deletion • PIK3R1 mutation
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fulvestrant • Aliqopa (copanlisib)
3ms
Enrollment closed • Enrollment change • Combination therapy
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ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PI3K (Phosphoinositide 3-kinases)
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ER positive • PIK3CA mutation • PTEN deletion • PIK3R1 mutation
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fulvestrant • Aliqopa (copanlisib)
5ms
Targeted DNA sequencing of recurrent glioblastoma identifies molecular factors associated with clinical outcomes (SNO 2023)
Salvage therapy comprised re-irradiation (n=52, 43%), temozolomide (TMZ) (n=39, 32%), lomustine (n=47, 39%), and/or bevacizumab (n=22, 18%). Our study outlines the molecular factors associated with survival and response to re-irradiation in rGBM as well as, the molecular differences between primary/recurrent samples.
Clinical • Clinical data • Tumor mutational burden
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TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MGMT (6-O-methylguanine-DNA methyltransferase) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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PTEN mutation • PDGFRA mutation • PIK3R1 mutation
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Avastin (bevacizumab) • temozolomide • lomustine
5ms
Circulating Tumor DNA as a Biomarker for ADCs in Metastatic Breast Cancer (SABCS 2023)
Notably, only one patient received sequential ctDNA testing, and in that case, there was a gain of TP53 p.N239S following sacituzumab govitecan administration compared to the baseline ctDNA test, followed by a gain of PIK3CA p.P449_L455del after trastuzumab deruxtecan administration. As we observe changes in subtypes following treatment progression, researchers are actively seeking biomarkers to better characterize real-time changes in tumor biology that can predict response and resistance to treatments. Further studies are needed to identify additional genes present in ctDNA that can provide mechanistic insights into why certain patients respond favorably to ADCs while others do not. We are currently enrolling patients for a prospective study that aims to assess baseline ctDNA levels and monitor changes in variant allele frequency following treatment with ADCs and immunotherapy.
IO biomarker • Circulating tumor DNA • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • FGFR4 (Fibroblast growth factor receptor 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • RHOA (Ras homolog family member A) • GATA3 (GATA binding protein 3) • HNF1A (HNF1 Homeobox A)
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HER-2 positive • TP53 mutation • KRAS mutation • HR positive • BRAF mutation • PIK3CA mutation • HER-2 expression • PTEN mutation • NF1 mutation • PIK3R1 mutation
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Tempus xF Assay
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Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy)
5ms
MOLECULAR CHARACTERIZATION OF STAGE I, GRADE 3 ENDOMETRIOID ENDOMETRIAL CANCER (IGCS 2023)
Seventy-five patients were identified. Unlike stage I, grade 1 EECs, which are mostly of copy number (CN)-low molecular subtype, most of our stage I, grade 3 EECs were of POLE (25/75, 33%) or microsatellite instability (MSI)-high (24/75, 32%) molecular subtypes; 20% (15/75) were CN-high and 15% (11/75) CN-low. Patients with MSI-high EECs, compared to other subtypes, were more likely to have deep myometrial invasion (p=0.02) and to have received chemotherapy (p=0.01).
MSi-H Biomarker
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • KMT2D (Lysine Methyltransferase 2D) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
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MSI-H/dMMR • PTEN mutation • POLE mutation • KMT2D mutation • MET mutation • PIK3R1 mutation
6ms
Pediatric Patients Aged 1 to 6 Years With APDS (clinicaltrials.gov)
P3, N=15, Recruiting, Pharming Technologies B.V. | Not yet recruiting --> Recruiting
Enrollment open
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PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta)
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PIK3R1 mutation
6ms
Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)
P2, N=100, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Aug 2033 --> Jan 2034 | Initiation date: Aug 2023 --> Jan 2024 | Trial primary completion date: Aug 2027 --> Jan 2028
Trial completion date • Trial initiation date • Trial primary completion date
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)
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PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation
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everolimus • Kisqali (ribociclib)
7ms
A New Type of Endometrial Cancer Models in Mice Revealing the Functional Roles of Genetic Drivers and Exploring their Susceptibilities. (PubMed, Adv Sci (Weinh))
The results reveal distinct vulnerabilities of ECs with different mutations. Taken together, this study develops a multiplexing approach to model EC in mice and demonstrates its value for understanding the pathology of and exploring the potential treatments for this malignancy.
Preclinical • Journal
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KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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KRAS mutation • PIK3CA mutation • KRAS G12D • KRAS G12 • PIK3R1 mutation
8ms
A comprehensive genomic study of 390 H3F3A-mutant pediatric and adult diffuse high-grade gliomas, CNS WHO grade 4. (PubMed, Acta Neuropathol)
Through our analysis, we were able to identify molecular features characteristic of DMG and DHG. By identifying the recurrent co-mutations including actionable FGFR1 point mutations found in nearly one-third of H3K27M-mutant DMG in young adults, our findings can inform clinical translational studies, patient diagnosis, and clinical trial design.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • H3-3A (H3.3 Histone A)
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PIK3CA mutation • NF1 mutation • CDKN2A deletion • FGFR1 mutation • CDK4 amplification • PIK3R1 mutation • CDK6 amplification
8ms
Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer. (PubMed, Exp Mol Med)
In particular, normal-like and luminal A subtypes in TNAC have much better DFS and OS than other intrinsic subtypes. Our findings are expected to impact medical practice for patients diagnosed with TNAC.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • PIK3CA mutation • PIK3R1 mutation • SBS5 signature
8ms
ROS1 alterations as a potential driver of gliomas in infant, pediatric, and adult patients. (PubMed, Mod Pathol)
We conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or co-driver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • PIK3CA mutation • PTEN mutation • CDKN2A deletion • ROS1 fusion • ROS1 positive • CDK4 amplification • PDGFRA mutation • GOPC-ROS1 fusion • IDH wild-type • MDM2 mutation • PIK3R1 mutation • CDK4 mutation
8ms
Clinical Features and Genetic Analysis of Taiwanese Primary Immunodeficiency Patients with Prolonged Diarrhea and Monogenetic Inflammatory Bowel Disease. (PubMed, J Clin Immunol)
When compared to those with the SD phenotype, the mono-IBD patients had significant early-onset and poor responses to empiric antibiotics, IVIG, and steroids. Anti-inflammatory biologics and suitable HSCT still have the potential to control or even cure the mono-IBD phenotype.
Journal
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PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CD (Phosphatidylinositol-4 5-Bisphosphate 3-Kinase Catalytic Subunit Delta) • FOXP3 (Forkhead Box P3) • STAT1 (Signal Transducer And Activator Of Transcription 1) • XIAP (X-Linked Inhibitor Of Apoptosis) • CD40LG (CD40 ligand) • RAG1 (Recombination Activating 1) • IL2RG (Interleukin 2 Receptor Subunit Gamma)
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PIK3R1 mutation
9ms
Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia. (PubMed, Blood Adv)
PIK3R1 deficiency leads to increased PI3K/AKT signaling which regulates cell cycle and the spliceosome machinery, both at the transcriptional and post-translational level. Moreover, several therapeutic combinations have been identified, where simultaneous targeting of the cyclin-dependent kinases 4 and 6 (CDK4/6) and NOTCH proved to be the most efficacious in T-ALL xenotransplantation models.
Journal • Combination therapy
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NOTCH1 (Notch 1) • CDK4 (Cyclin-dependent kinase 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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NOTCH1 mutation • PIK3R1 mutation
10ms
Expanding the spectrum of TERT promoter non-canonical sequence variants in brain tumors: A case series (AANP 2023)
The tumor with c.-92_-91ins had NF1/PIK3CA mutations; the case with c.-123_-76dup had PTEN/MYCN mutations and chromosome 7 gain/10 loss/CDK4, MDM2 amplification; and the tumor with c.-118_-117ins had a CBL mutation. Conclusions Our findings expand the spectrum of TERTp non-canonical variants in brain tumors and further suggest that they typically occur in tumors with features of GBM-IDHWT as a clinically/diagnostically relevant alternative TERTp activating mechanism.
Clinical
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • STAG2 (Stromal Antigen 2)
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TP53 mutation • EGFR mutation • PIK3CA mutation • PTEN mutation • NF1 mutation • MDM2 amplification • CBL mutation • CDK4 amplification • STAG2 mutation • TERT mutation • IDH wild-type • PIK3R1 mutation • CDK4 mutation
10ms
Triple-Negative Apocrine Carcinomas: Toward a Unified Group With Shared Molecular Features and Clinical Behavior. (PubMed, Mod Pathol)
Divergent genetic profiles between A-DCIS and invasive carcinoma were identified in 1 case. In summary, our findings support TNAC as a morphologically, immunohistochemically, and genetically homogeneous subgroup of triple-negative breast carcinomas and suggest overall favorable clinical behavior.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AR (Androgen receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • ARID2 (AT-Rich Interaction Domain 2) • SOX10 (SRY-Box 10) • GATA3 (GATA binding protein 3) • TRPS1 (Transcriptional Repressor GATA Binding 1)
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TP53 mutation • PIK3CA mutation • NF1 mutation • RAS mutation • AR expression • PIK3R1 mutation
10ms
Molecular Landscape of Mullerian Clear Cell Carcinomas Identifies The Cancer Genome Atlas-like Prognostic Subgroups. (PubMed, Mod Pathol)
On multivariable analysis, stage, lymphovascular invasion, and tumor mutational burden were prognostic for disease-free survival, whereas advanced stage and TP53-mutant subgroup - but not a TP53 mutation in isolation - were negative prognostic factors for overall survival. These data suggest that routine molecular profiling of Mullerian CCC may be warranted for both prognosis and identification of potential targeted treatments, such as immunotherapy and anti-HER2 agents.
Retrospective data • Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • TERT (Telomerase Reverse Transcriptase) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • MSI-H/dMMR • HER-2 amplification • PIK3CA mutation • PTEN mutation • ARID1A mutation • TERT mutation • ER expression • PIK3R1 mutation • TERT promoter mutation
11ms
Superselective Intra-arterial Cerebral Infusion of Temsirolimus in HGG (clinicaltrials.gov)
P1, N=12, Recruiting, Nader Sanai | Not yet recruiting --> Recruiting
Enrollment open
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • mTOR (Mechanistic target of rapamycin kinase) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta)
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PIK3CA mutation • MTOR mutation • PIK3CA mutation + PTEN mutation • PIK3R1 mutation
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Torisel (temsirolimus)
11ms
Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)
P2, N=100, Not yet recruiting, Nationwide Children's Hospital
New P2 trial
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)
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PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation
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everolimus • Kisqali (ribociclib)
1year
PIK3CA and PIK3R1 tumor mutational landscape in a pan-cancer patient cohort and its association with pathway activation and treatment efficacy. (PubMed, Sci Rep)
In ER+/HER2- mBC, first line chemotherapy efficacy was similar for PIK3CA-mutated and PIK3CA-WT tumors, whereas in triple negative mBC, chemotherapy appeared to be more effective in PIK3CA-WT tumors. In this large, real-life pan-cancer patient cohort, our results indicate that PIK3CA/PIK3R1 mutations are widely spread, and plead in favour of evaluating the efficacy of PI3K inhibitors outside of ER+/HER2- mBC and outside of hotspot mutations.
Journal • Pan tumor
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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HER-2 negative • PIK3CA mutation • PIK3R1 mutation
1year
New P1 trial
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • mTOR (Mechanistic target of rapamycin kinase) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta)
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PIK3CA mutation • MTOR mutation • PIK3CA mutation + PTEN mutation • PIK3R1 mutation
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Torisel (temsirolimus)
1year
Activity of targeted agents in PIK3R1 mutated patient-derived xenografts (AACR 2023)
We previously reported that breast cancer cells lacking protein expression of PIK3R1 had elevated levels of activated MEK, sensitizing them to the MEK inhibitor trametinib. Mutations in PIK3R1 sensitize TNBCs to MEK inhibitors like binimetinib. In the absence of functional PIK3R1, aberrant PI3K signaling occurs, which explains the sensitivity of breast cancers that are PIK3CA wild-type and PIK3R1 mutant to alpelisib. The combination of both MEK and PIK3CA inhibition appears to be an effective combination therapy in TNBCs harboring mutations in PIK3R1.AMA is employed by the U.S. FDA, but contributed to this publication in his own capacity.
Clinical
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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PIK3CA mutation • PTEN mutation • PIK3CA wild-type • PIK3R1 mutation
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Mekinist (trametinib) • Piqray (alpelisib) • Mektovi (binimetinib)
1year
TERT Promoter Mutation c.-124C>T Commonly Occurs in Low-Grade Fibromatosis-like Metaplastic Breast Carcinoma. (PubMed, Arch Pathol Lab Med)
In conjunction with previous data of metaplastic (spindle cell) carcinoma with and without fibromatosis-like morphology, FLMC is most likely distinguished by TERT promoter mutation. Thus, our data support the notion of a distinct subgroup within low-grade metaplastic breast cancer with spindle cell morphology and associated TERT mutations.
Journal • Tumor mutational burden
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • PIK3CA mutation • TP53 wild-type • TMB-L • CDKN2A mutation • MTOR mutation • TERT mutation • PIK3R1 mutation • TERT promoter mutation • TERT 124C>T
1year
Comprehensive Kinase Activity Profiling Revealed the Kinase Activity Patterns Associated with the Effects of EGFR Tyrosine Kinase Inhibitor Therapy in Advanced Non-Small-Cell Lung Cancer Patients with Sensitizing EGFR Mutations. (PubMed, Proteomes)
Patients with poor prognoses exhibited high activation of EGFR, PIK3R1, and ERBB2. Comprehensive kinase activity profiles may provide predictive biomarker candidates for screening patients with advanced NSCLC harboring sensitizing EGFR mutations.
Journal • Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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EGFR mutation • PIK3R1 mutation
1year
New trial • Liquid biopsy • Biopsy
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • MUC4 (Mucin 4, Cell Surface Associated)
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HER-2 positive • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 mutation • PIK3R1 mutation
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Kadcyla (ado-trastuzumab emtansine)
1year
Fistula-Associated Anal Adenocarcinoma: A 20-Year Single-Center Experience. (PubMed, Ann Surg Oncol)
FAAC is rare but associated with poor clinical outcome. Tissue acquisition is crucial for early diagnosis and therapy and should be performed in long-standing, non-healing, IBD-associated fistulas in particular. The immunophenotype of FAAC seems more similar to the rectal-type mucosa than the anal glands.
Journal
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TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • SMAD4 (SMAD family member 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • NOTCH3 (Notch Receptor 3) • CDX2 (Caudal Type Homeobox 2) • MUC2 (Mucin 2)
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TP53 mutation • ATM mutation • NOTCH3 mutation • PIK3R1 mutation
1year
Spectrum and clinical features of gene mutations in Chinese pediatric acute lymphoblastic leukemia. (PubMed, BMC Pediatr)
This study depicted the specific genomic landscape of Chinese pediatric ALL and revealed the relevance between mutational spectrum and clinical features of Chinese pediatric ALL, which highlights the need for molecular classification, risk stratification, and prognosis evaluation.
Journal
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KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NOTCH1 (Notch 1) • ETV6 (ETS Variant Transcription Factor 6) • KMT2D (Lysine Methyltransferase 2D) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PHF6 (PHD Finger Protein 6)
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KRAS mutation • FLT3 mutation • PTEN mutation • NOTCH1 mutation • KMT2D mutation • PHF6 mutation • PIK3R1 mutation
1year
Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study. (PubMed, Lancet Oncol)
Not all mutations related to TMB-H can enhance antitumour immune response. More composite biomarkers should be investigated (eg, mTMB signature) to tailor treatment with immune checkpoint inhibitors. Our data also provide novel insights for the combination of immune checkpoint inhibitors and drugs targeting cyclin D1 or FGFs.
Retrospective data • Journal • Tumor mutational burden • MSi-H Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • JAK2 (Janus kinase 2) • KEAP1 (Kelch Like ECH Associated Protein 1) • RUNX1 (RUNX Family Transcription Factor 1) • mTOR (Mechanistic target of rapamycin kinase) • CCND1 (Cyclin D1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • STAG2 (Stromal Antigen 2) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • CTNNA1 (Catenin Alpha 1) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) • SMAD2 (SMAD Family Member 2)
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TMB-H • MSI-H/dMMR • TMB-L • KEAP1 mutation • MTOR mutation • PIK3R1 mutation
1year
A Phase 0 /II Study of Ribociclib (LEE011) in Combination With Everolimus in Preoperative Recurrent High-Grade Glioma Patients Scheduled for Resection (clinicaltrials.gov)
P1, N=27, Completed, St. Joseph's Hospital and Medical Center, Phoenix | Active, not recruiting --> Completed | Trial completion date: Jul 2022 --> Feb 2022 | Trial primary completion date: Jun 2022 --> Feb 2022
Trial completion • Trial completion date • Trial primary completion date • Combination therapy
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • mTOR (Mechanistic target of rapamycin kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta)
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PIK3CA mutation • CCND1 amplification • CDK4 amplification • MTOR mutation • PIK3CA mutation + PTEN mutation • PIK3R1 mutation
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everolimus • Kisqali (ribociclib)
1year
High Tumor Mutational Burden Predicts Recurrence in Copy Number Low Early Stage Endometrial Cancer and is Associated with ARID1A and TP53 Mutations: Practical Implications for ARID1A and P53 Immunostaining as a Triage Tool (USCAP 2023)
High TMB is present in 23% of CN-L EC, associated with ARID1A and TP53 mutations and recurrence in low grade, early stage disease. These results identify ARID1A and p53 immunohistochemistry as potential prognostic markers or triage tools for TMB testing via NGS in early stage endometrioid carcinoma.
Tumor mutational burden
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • TMB-H • PTEN mutation • ARID1A mutation • TMB-L • CTNNB1 mutation • PIK3R1 mutation
1year
Neoadjuvant Chemotherapy for Luminal Androgen Receptor (LAR) Breast Cancer: Potential Predictive Biomarkers and Genetic Alterations (USCAP 2023)
This study indicated that the LAR phenotype is associated with lower rates of pCR after NACT. Our results suggest that assessment of FOXC1 in LAR patients may be applied as a predictive marker for the efficacy of NACT,and highlights the genetic basis in non-pCR LARs and provides a rationale for the AR inhibitor and PI3K/AKT/mTOR inhibitors in these tumors.
Clinical
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • TSC2 (TSC complex subunit 2) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • FOXC1 (Forkhead Box C1)
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PIK3CA mutation • PTEN mutation • AR positive • AKT1 mutation • TSC2 mutation • AR expression • PIK3R1 mutation • AR negative • FOXC1 expression
over1year
Potential Drivers of Acquired Resistance to Idelalisib in CLL Patients (ASH 2022)
We checked the phosphorylation/activation level of AKT and ERK1/2 at the responding and progression time points in the three original CLL patients with acquired resistance and observed that pERK levels are inhibited by idelalisib at baseline, but not at progression, in 2 patients (patient 1 and 2). In conclusion, we have identified potential drivers of acquired resistance to idelalisib in CLL patients, including MAPK pathway activation as in our prior study, and we continue with ongoing work evaluating the potential role of PI3K pathway mutations, BIRC3, AICDA and LTK in treatment resistance, since insights from these studies will help us guide therapy for CLL patients with refractory disease.
Clinical • Preclinical • BRCA Biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CD79B (CD79b Molecule) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • BIRC3 (Baculoviral IAP repeat containing 3) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • IKZF3 (IKAROS Family Zinc Finger 3) • LTK (Leukocyte Receptor Tyrosine Kinase) • NFATC1 (Nuclear Factor Of Activated T Cells 1) • PDIA3 (Protein Disulfide Isomerase Family A Member 3) • DDX3X (DEAD-Box Helicase 3 X-Linked) • NFATC3 (Nuclear Factor Of Activated T Cells 3)
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TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • ATM mutation • RAS mutation • SF3B1 mutation • BIRC3 mutation • PIK3R1 mutation
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Zydelig (idelalisib)
over1year
High Prevalence of Epigenetic Mutations in Histiocytic and Dendritic Cell Disorders: Results from Molecular Analysis of a Large Cohort from Histiocytosis Working Group (ASH 2022)
These mutations were specifically enriched in tumors with non-BRAF-V600E mutations, and in MRH/MH. These data shed light on additional mechanisms of disease pathogenesis, and with available epigenetic therapies, warrant further investigation.
KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ARID1A (AT-rich interaction domain 1A) • mTOR (Mechanistic target of rapamycin kinase) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • INPP4B (Inositol polyphosphate-4-phosphatase type II B) • CSF1R (Colony stimulating factor 1 receptor) • PI3K (Phosphoinositide 3-kinases) • PIK3R2 (Phosphoinositide-3-Kinase Regulatory Subunit 2 ) • PIK3R3 (Phosphoinositide-3-Kinase Regulatory Subunit 3)
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BRAF V600E • KRAS mutation • NRAS mutation • PIK3CA mutation • ARID1A mutation • KMT2D mutation • MTOR mutation • PIK3R1 mutation
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Tempus xT Assay
over1year
Molecular Evidence for Epithelial Origin of Mixed Ovarian Epithelial-Germ Cell Neoplasms: Report of 2 Cases and Review of Literature. (PubMed, Int J Gynecol Pathol)
These mutational patterns are similar to those seen in pure epithelial counterparts, suggesting somatic derivation of the germ cell component. These rare tumors portend a poor prognosis and understanding their origin has clinical and therapeutic implications.
Review • Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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PTEN mutation • PIK3R1 mutation
over1year
Targeted Next-Generation Sequencing Panel Reveals Differences in Mutational Patterns between Endometrial Cancer Molecular Classifier Subgroups (AMP 2022)
Our findings from real-world implementation of ProMise classification are consistent with prior studies. All subgroups had mutations in genes implicated in PI3K pathway activation, with >95% of tumors within the POLE, MMRd, and NSMP subgroups altered. aTP53 tumors harbored fewer PI3K pathway mutations than the other subgroups.
Next-generation sequencing • Tumor Mutational Burden
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • KRAS mutation • PIK3CA mutation • PTEN mutation • FGFR2 mutation • POLE mutation • CTNNB1 mutation • AKT1 mutation • PIK3R1 mutation
over1year
Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia. (PubMed, Hemasphere)
Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.
Journal
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KMT2A (Lysine Methyltransferase 2A) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • PAX5 (Paired Box 5) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
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TP53 mutation • KRAS mutation • NRAS mutation • PIK3CA mutation • RAS mutation • KMT2A rearrangement • MLL rearrangement • PIK3R1 mutation