News - PTEN mutation - LARVOL VERI

Crosstalk between CD180-overexpression macrophages and glioma cells worsens patient survival through malignant phenotype promotion and immunosuppressive regulation. (PubMed, Mol Med)

This study confirmed the prognostic role of CD180 in glioma and its involvement in immunosuppressive regulation and malignant phenotype promotion. Therefore, CD180 was considered as a promising target for immunotherapeutic strategies in glioma treatment.

1 day ago

Journal • IO biomarker

PTEN (Phosphatase and tensin homolog)

TP53 mutation • PTEN mutation

IDENTIFICATION OF CLINICALLY RELEVANT GENE VARIANTS IN COLON ADENOCARCINOMA SAMPLES OF UKRAINIAN PATIENTS USING A COMPREHENSIVE CANCER PANEL: A PILOT STUDY. (PubMed, Exp Oncol)

These data suggest a high level of clinical relevance of the NGS CCP approach. Further confirmation on a larger number of samples and using a deeper analysis by other approaches is required.

2 days ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • SMAD4 (SMAD family member 4) • APC (APC Regulator Of WNT Signaling Pathway) • CHEK2 (Checkpoint kinase 2) • FLCN (Folliculin) • SMAD2 (SMAD Family Member 2) • TCF12 (Transcription Factor 12)

TP53 mutation • KRAS mutation • PTEN mutation • CHEK2 mutation • AKT1 mutation

Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules (clinicaltrials.gov)

P1, N=285, Completed, AstraZeneca | Active, not recruiting --> Completed

3 days ago

Trial completion • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)

ER positive • PIK3CA mutation • PTEN mutation • AKT1 mutation

fulvestrant • Truqap (capivasertib)

Molecular profile of adult primary leptomeningeal gliomatosis aligns with glioblastoma, IDH-wildtype. (PubMed, Brain Pathol)

Only one case, with relatively localized disease at diagnosis, received chemoradiation therapy and survived 535 days, raising the possibility that early diagnosis and timely treatment could improve outcome. A detailed list of previously reported cases is provided in a supplementary table.

5 days ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • GLI1 (GLI Family Zinc Finger 1)

TP53 mutation • PTEN mutation • CDKN2A deletion • CDK4 amplification • TERT mutation • TERT promoter mutation

Genomic characterization and histologic analysis of uterine leiomyosarcoma arising from leiomyoma with bizarre nuclei. (PubMed, J Pathol)

5 days ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

PTEN mutation • CDKN2A deletion

Testing the Addition of Copanlisib to Eribulin for the Treatment of Advanced-Stage Triple Negative Breast Cancer (clinicaltrials.gov)

P1/2, N=106, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

5 days ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog)

HER-2 amplification • HER-2 negative • PIK3CA mutation • PTEN mutation

Halaven (eribulin mesylate) • Aliqopa (copanlisib)

PIK3CA Mutations and Co-Mutations in Operated Non-Small Cell Lung Carcinoma. (PubMed, J Clin Med)

The top 10 mutations that most commonly accompanied PIK3CA variations were KRAS, NF1, TP53, EGFR, PTEN, BRAF, KIT, CDKN2A, SMARCA4, and ATM mutations, respectively. PIK3CA variations, along with other gene variations, may influence cancer progression and thus may play a crucial role in the determination of targeted treatment strategies.

5 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • 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) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)

TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • ATM mutation • PIK3CA H1047R • PTEN mutation • PIK3CA E545K • CDKN2A mutation • SMARCA4 mutation • PIK3CA E545 • PIK3CA E542

Genomic Profiling in Glioma Patients to Explore Clinically Relevant Markers. (PubMed, Int J Mol Sci)

In IDH-wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS...Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.

5 days ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler)

TP53 mutation • PIK3CA mutation • IDH1 mutation • PTEN deletion • PTEN mutation • TERT mutation • IDH mutation + Chr del(1p) + Chr del(19q)

Avastin (bevacizumab)

Next-generation sequencing in the molecular classification of endometrial carcinomas: Experience with 270 cases suggesting a potentially more aggressive clinical behavior of multiple classifier endometrial carcinomas. (PubMed, Virchows Arch)

Our findings suggest that combining immunohistochemistry with NGS offers a more reliable classification of ECs, including 'multiple classifier' cases, which, based on our observations, tend to exhibit aggressive behavior. Additionally, our data highlight the complex genetic background of NSMP ECs, which can facilitate further stratification of tumors within this group and potentially help select patients for dedicated clinical trials.

7 days ago

Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)

TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation

Association of Oncogene Driver Mutations with Recurrence and Survival in Stage I Nonsmall Cell Lung Cancer. (PubMed, Clin Lung Cancer)

Oncogene mutations such as KRAS G12V and EGFR may have implications for cancer surveillance strategies and inform future treatment trials of stage I NSCLC.

8 days ago

Journal

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog)

TP53 mutation • KRAS mutation • EGFR mutation • PTEN mutation • KRAS G13D • MET mutation • KRAS G12 • KRAS G13

10d

Negative response to immunotherapy in dMMR or MSI-H gastric cancer with APC and PTEN mutations: a case report. (PubMed, Front Oncol)

We attempted to elucidate the underlying causes and mechanisms behind this lack of response, and to provide new insights into treatment options for these patients. Mutations of key genes within tumor-related signaling pathways and the infiltration of CD8+T cells in the tumor microenvironment may influence the efficacy of immunotherapy for MSI-H solid tumors.

10 days ago

Journal • Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • CD8 (cluster of differentiation 8) • APC (APC Regulator Of WNT Signaling Pathway)

PD-L1 expression • TMB-H • MSI-H/dMMR • PD-L1 overexpression • PTEN deletion • PTEN mutation • APC mutation

11d

Carboplatin With or Without Atezolizumab in Treating Patients With Stage IV Triple Negative Breast Cancer (clinicaltrials.gov)

P2, N=106, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed

11 days ago

Trial completion • Tumor mutational burden • IO biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BRCA (Breast cancer early onset) • INPP4B (Inositol polyphosphate-4-phosphatase type II B)

HER-2 negative • PIK3CA mutation • PTEN mutation

Tecentriq (atezolizumab) • carboplatin

12d

Pleiotropic tumor suppressive functions of PTEN missense mutations during gliomagenesis. (PubMed, iScience)

Moreover, expression of these PTEN mutations heightened EGFR activity by sequestering EGFR within endomembranes longer and affected its signaling behavior. Through comprehensive studies on global protein phosphorylation and kinase library analyses in cells with the G36E and L42R PTEN mutations, we identified distinct cancer-promoting pathways activated by EGFR, offering targets for treating GBM with these PTEN alterations.

12 days ago

Journal

EGFR (Epidermal growth factor receptor) • PTEN (Phosphatase and tensin homolog)

EGFR mutation • PTEN mutation • PTEN expression

16d

Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With BRCA Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy. (PubMed, JCO Precis Oncol)

In real-world setting, substantially lower OS in mCRPC is observed for BRCA- and PTEN/TP53/RB1-mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA-treated patients, worst outcomes were observed for BRCA patients.

16 days ago

Journal • BRCA Biomarker • Metastases

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • BRCA (Breast cancer early onset)

TP53 mutation • PTEN mutation • RB1 mutation • BRCA mutation

16d

Newcastle disease virus harboring the PTEN gene inhibits pancreatic cancer growth by inhibiting PI3K/AKT/mTOR signaling and activating apoptosis. (PubMed, Mol Ther Oncol)

These findings support the potential of rNDV-PTEN as a safe and effective therapy for PDAC with highly activated PI3K/AKT/mTOR signaling caused by KRAS and PTEN gene mutations. Thus, PTEN gene-containing rNDV may be a promising candidate for pancreatic cancer treatment.

16 days ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog)

KRAS mutation • PTEN mutation • PTEN expression

16d

Comprehensive gene set enrichment and variation analyses identify SUV39H1 as a potential prognostic biomarker for glioblastoma immunorelevance. (PubMed, Comput Struct Biotechnol J)

Inhibition of SUV39H1 restrains GBM growth and reduces the stem cell properties of GSC. Thus, SUV39H1 might be a prognostic predictor and immunotherapeutic target in patients with GBM.

16 days ago

Journal • IO biomarker

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • SOX2 • IL18 (Interleukin 18) • NES (Nestin) • CRYAB (Crystallin Alpha B) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1) • SUV39H1 (SUV39H1 Histone Lysine Methyltransferase)

TP53 mutation • PTEN mutation • PTEN expression

18d

Molecular characterization of ovarian squamous cell carcinoma originating from mature teratoma. (PubMed, J Mol Med (Berl))

TP53 mutations found in 82% of ovarian SCC cases. CDKN2A mutations and 9p21.3 loss observed in 54.5% of ovarian SCC cohort.

18 days ago

Journal

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) • KMT2D (Lysine Methyltransferase 2D)

TP53 mutation • PIK3CA mutation • PTEN mutation • CDKN2A mutation • KMT2D mutation

19d

Uterine sarcoma with KAT6B/A::KANSL1 fusion: a molecular and clinicopathological study on 9 cases. (PubMed, Virchows Arch)

Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

19 days ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • TSC1 (TSC complex subunit 1) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCD2 (FA Complementation Group D2) • KAT6B (Lysine Acetyltransferase 6B)

TP53 mutation • ATM mutation • PTEN mutation • NF1 mutation • TSC1 mutation • PDGFRB mutation

19d

Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response Pathway-Deficient Neoplasms. (PubMed, JCO Precis Oncol)

Niraparib failed to meet the prespecified efficacy end point for response. However, clinical benefit was suggested in a proportion of patients who had a confirmed mBAP1, supporting further investigation.

19 days ago

P2 data • Journal • BRCA Biomarker • PARP Biomarker

PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein)

PTEN mutation • ARID1A mutation • BAP1 mutation

Zejula (niraparib)

20d

A real-world study of first-line albumin-bound paclitaxel in the treatment of advanced pancreatic cancer in China (PubMed, Zhonghua Zhong Liu Za Zhi)

Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death (P＜0.05). Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

20 days ago

Journal • Real-world evidence • Real-world • Metastases

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • RBBP8 (RB Binding Protein 8, Endonuclease)

TP53 mutation • KRAS mutation • PTEN mutation

albumin-bound paclitaxel

21d

POLE-mutated uterine carcinosarcomas: a clinicopathologic and molecular study of 11 cases. (PubMed, Mod Pathol)

Our study supports full molecular classification of UCS. We also raise awareness for potentially assessing POLE mutation allele fraction and clonality in the consideration of classifying a tumor as POLEmut.

21 days ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

TP53 mutation • PIK3CA mutation • PTEN mutation • ARID1A mutation • POLE mutation • TP53 expression

26d

Endometrial Atypical Hyperplasia and Risk of Endometrial Cancer. (PubMed, Diagnostics (Basel))

Biomarkers and minimally invasive surgical techniques are emerging as promising approaches in improving outcomes for women with EAH. This review underscores the importance of early diagnosis and personalized management in preventing the progression of EAH to EC, highlighting current clinical practices and potential future developments in this field.

26 days ago

Review • Journal

KRAS (KRAS proto-oncogene GTPase) • PTEN (Phosphatase and tensin homolog)

KRAS mutation • PTEN mutation

26d

Novel Fibroblast Growth Factor Receptor 3-Fatty Acid Synthase Gene Fusion in Recurrent Epithelioid Glioblastoma Linked to Aggressive Clinical Progression. (PubMed, Curr Oncol)

Postoperative treatment included radiotherapy and temozolomide...The recurrence was managed with regorafenib and bevacizumab, though complications like hand-foot syndrome and radiation necrosis arose...The novel FGFR3-FASN fusion suggests potential implications for GBM recurrence and lipid metabolism. Further studies are warranted to explore FGFR3-FASN's role in GBM and its therapeutic targeting.

26 days ago

Journal

PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FASN (Fatty acid synthase)

IDH2 mutation • PTEN deletion • PTEN mutation • CDKN2A deletion • CDKN2A mutation • TERT mutation • TERT promoter mutation

Avastin (bevacizumab) • temozolomide • Stivarga (regorafenib)

26d

The Evolving Molecular Landscape and Actionable Alterations in Urologic Cancers. (PubMed, Curr Oncol)

We also emphasize the importance of biomarker identification for personalized management, especially in metastatic settings where treatment intensification is often required. Future research is needed to further elucidate our understanding of the genetics affecting urologic cancers, which will help develop novel, individualized therapies to enhance oncologic outcomes.

26 days ago

Review • Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

BRCA2 mutation • BRCA1 mutation • PD-L1 overexpression • PTEN mutation

Risk factors for and molecular pathology characteristics of systemic metastasis of adult cerebral glioblastoma: A pooled individual patient data analysis and systematic review. (PubMed, J Neurol Surg A Cent Eur Neurosurg)

Conclusion In young adult GBM patients, especially those ≤ 40 years of age with long survival, attention should be given to the development of systemic metastases. Metastasis can be the result of multiclonal gene mutations, in which proliferation- and invasion-related gene changes, such as oncogene or tumor suppressor gene mutations and epithelial-mesenchymal transition-related genes, may play an important role in metastasis.

1 month ago

Review • Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • TERT (Telomerase Reverse Transcriptase)

TP53 mutation • PTEN mutation • RB1 mutation • TERT mutation • IDH wild-type • TERT promoter mutation

Pathologists' integration of prior biopsies of women with germline PTEN mutations may expedite the identification of this rare cancer predisposition syndrome. (PubMed, Pathology)

Other neoplasms included endometrial carcinoma (two patients) and dysplastic cerebellar gangliocytoma (three patients). Integrating the biopsy histories of PTEN P/LP variant carriers over time may assist in raising the possibility of an underlying cancer susceptibility syndrome, so appropriate clinical and genetic counselling and evaluation may be considered.

1 month ago

Journal • Biopsy

PTEN (Phosphatase and tensin homolog)

PTEN mutation

Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan. (PubMed, Cancer Med)

This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.

1 month ago

Journal • Tumor mutational burden • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q)

BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • PTEN mutation • BRAF V600K • TMB-L • NF1 mutation

Prognostic significance of actionable next-generation sequencing multigene panel in esophageal cancer treatment. (PubMed, Eur Rev Med Pharmacol Sci)

The utility of an actionable multigene panel revealed the value of a well-designed NGS workflow in the practical use of clinical outcomes via the prediction of responsiveness to therapeutic agents or indications for novel treatment modalities in addition to the estimation of prognosis.

1 month ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • NTRK (Neurotrophic receptor tyrosine kinase)

PTEN mutation

Next-generation sequencing uncovers crucial mutated genes and potential therapeutic targets in ovarian cancer patients. (PubMed, Am J Transl Res)

These findings provide novel insights into the genetic underpinnings of ovarian cancer in the Pakistani population and suggest potential targets for therapeutic intervention.

1 month ago

Journal • Next-generation sequencing • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2)

BRCA2 mutation • BRCA1 mutation • PTEN mutation • BRCA1 mutation + BRCA2 mutation • BRCA1 expression

PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma (rGBM) (AIOM 2024)

Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations.

1 month ago

Clinical

PTEN (Phosphatase and tensin homolog) • MGMT (6-O-methylguanine-DNA methyltransferase)

PTEN mutation • IDH wild-type

FoundationOne® CDx

Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)

A novel machine learning model integrating clinical and molecular data to predict response to second line treatment in recurrent IDHwtglioblastoma (AIOM 2024)

Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.

1 month ago

Clinical • Machine learning

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • EGFR mutation • PTEN mutation • IDH wild-type • MTAP mutation

FoundationOne® CDx

Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)

Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)

Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.

1 month ago

Clinical • Next-generation sequencing • BRCA Biomarker • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)

BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification

FoundationOne® CDx • TruSight Oncology 500 Assay

PIK3CA mutations in endometrial cancer: a pre-planned biomarker analysis from the phase II MITO END-3 study of carboplatin and paclitaxel with or without avelumab in advanced or recurrent endometrial cancer (AIOM 2024)

The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.

1 month ago

P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases

TP53 (Tumor protein P53) • 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)

TP53 mutation • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PIK3CA H1047R • PTEN mutation • ARID1A mutation • POLE mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + PTEN mutation • PIK3CA C420R • PIK3CA E545A • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546R

FoundationOne® CDx

carboplatin • paclitaxel • Bavencio (avelumab)

Liquid biopsy-based comprehensive genomic profiling captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAFV600E wild type metastatic colorectal cancer in the CAPRI 2-GOIM trial (AIOM 2024)

Materials and The phase II CAPRI 2-GOIM trial investigates the efficacy and safety of biomarkerdriven, cetuximab-based, sequence of three treatment lines in mCRC... Baseline plasma-based comprehensive genomic profiling is feasible with high concordance with tissue-based analysis. Liquid biopsy allows identification of misdiagnosed RAS/BRAF alterations and the ultra-selection of pts, which could benefit from anti-EGFR therapies. Finally, potentially actionable gene alterations were found in half of the pts.

1 month ago

Clinical • Late-breaking abstract • Liquid biopsy • Metastases • Biopsy

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • RAS (Rat Sarcoma Virus)

BRAF V600E • KRAS mutation • HER-2 amplification • NRAS mutation • BRAF V600 • PTEN mutation • BRAF wild-type • NF1 mutation • EGFR amplification + ERBB2 amplification

FoundationOne® CDx

Erbitux (cetuximab)

Advantages of next-generation sequencing (NGS) in the molecular classifi cation of endometrial carcinomas - our experience with 270 cases. (PubMed, Ceska Gynekol)

In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.

1 month ago

Journal • Next-generation sequencing • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • 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) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • POLD1 (DNA Polymerase Delta 1)

TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation

Identification of cancer driver mutations in liquid-based cytology samples for the screening of endometrial diseases. (PubMed, BJC Rep)

The genetic analysis combined with liquid-based cytology is useful to improve the diagnostic sensitivity of endometrial neoplasms. However, caution must be taken when cancer-associated mutation(s) are detected in the genetic analysis. Further investigation may clarify the risk of malignant endometrial neoplasms in women with driver mutation(s).

1 month ago

Journal • Cytology

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • PTEN mutation • CTNNB1 mutation

Quantifying neurobehavioral profiles across neurodevelopmental genetic syndromes and idiopathic neurodevelopmental disorders. (PubMed, Dev Med Child Neurol)

Genetic syndromes associated with neurodevelopmental disorders present with unique neurobehavioral profiles that can inform selection of outcome measures in future clinical trials. The NET may be a useful screening and monitoring instrument in clinical practice, where frequent in-person clinic attendance is difficult for many patients.

1 month ago

Journal

PTEN (Phosphatase and tensin homolog)

PTEN mutation

NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov)

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

1 month ago

Trial completion date • Trial primary completion date • IO biomarker

PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2)

BRAF V600E • BRAF mutation • BRAF V600 • PTEN mutation • BRAF V600K

THXID® BRAF Kit • cobas® 4800 BRAF V600 Mutation Test

Mekinist (trametinib) • Tafinlar (dabrafenib) • navitoclax (ABT 263) • omipalisib (GSK2126458)

Diagnostic and Clinical Utility of OncoScan Microarray and NGS-Based Sequencing in Pediatric Solid Tumors: Children's Mercy Hospital Experience (AMP 2024)

OS+ is a reliable test to identify clinically relevant genomic alterations, cnLOH, and several hotspot mutations in pediatric FFPE solid tumor specimens. WGS/WES significantly increases the yield of actionable somatic mutations and cancer-predisposing germline variants. The cost, turnaround time, and tumor percentage in the specimen make OS+ followed by WES principal tests for pediatric solid tumor analysis at our institution.

1 month ago

Clinical • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NF1 (Neurofibromin 1) • MLH1 (MutL homolog 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • H3-3A (H3.3 Histone A)

TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • PIK3CA mutation • BRAF V600 • PTEN mutation • BRAF fusion

OncoScan™ CNV Assay

Low Limit of Detection Increases Detection and Reporting of Actionable Genomic Alterations (AMP 2024)

The ability to detect SNVs and indels below 5% VAF increases the diagnostic yield of actionable genomic alterations. This enables additional patients to consider FDA-approved on-label targeted therapies as a treatment option. Taken together, CGP assays that couple high sensitivity and low LOD can maximize identification of therapeutically relevant alterations across solid tumor types.

1 month ago

BRCA Biomarker

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

BRAF V600 • PTEN mutation

OncoExTra™ test

Genomic Landscape of Fusions in Solid Tumors Detected by DNA and RNA Comprehensive Genomic Profiling at a Large Community Health System (AMP 2024)

The routine use of RNA-based CGP analysis allows for the comprehensive detection of oncogenic fusions in patients with cancer. The diversity of tumor types in which actionable fusions were detected supports the broader utilization of CGP to potentially increase targeted therapy usage and improve outcomes across cancer subtypes.

1 month ago

Tumor mutational burden

ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)

TMB-H • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • PTEN mutation • ALK fusion

TruSight Oncology 500 Assay

Geographic variation of Decipher risk score and underlying transcriptomic in patients with post prostatectomy early prostate cancer (EMUC 2024)

Similarly, PSC basal-luminal shows the basal neuroendocrine-like is much higher in Israeli cohort 27% vs 7.5% (p=0.004). Conclusions These preliminary results suggest that geographic variation of decipher genomic classifier risk score in patients with early prostate cancer may exist, and correlate with differences in transcriptomic profile, including androgen receptor activity, p53 mutation, pTEN tumor suppressor gene deletion, and basal-luminal biologic phenotype.

1 month ago

Clinical

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog)

TP53 mutation • PTEN mutation • AR mutation

Prosigna™ Breast Cancer Prognostic Gene Signature Assay • Decipher Prostate Cancer Test