PTEN mutation

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.

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.

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.

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.

We also identified several samples with high mutation burden between ADAR1 and other genes regulated primarily in endometrial cancers. Finally, we show that the deaminase domain is highly conserved in metazoans and mutations within conserved residues do occur in human cancers suggesting that destabilization of the enzyme function is contributing to cancer development.

These results are crucial for characterizing candidates for AKT pathway-targeted molecular therapies and conceptualizing optimal treatment strategies. Clinical trial registration: This study is an observational study and is therefore not registered with the clinical trials registration.

This pilot study explores the applicability of LB in GEP-NETs MP evaluation. Further studies with larger cohorts are needed to validate LB and to define the clinical impact.

Furthermore, this review explores the expression and regulation of PTEN in different tumor types, as well as its interactions with environmental factors in tumorigenesis. This comprehensive analysis aims to deepen our understanding of the signaling pathways between PTEN and cancer.

The study found that leptin signalling impairment and insulin resistance, as well as mutations in CYP1A1, CYP19A1, ESR1, AR, AMH, AdipoR1, NAMPT, NPY, PTEN, EGFR, and Akt, all play significant roles in PCOS in the studied group. Young women in West Bengal, India, are more likely to have co-occurring PCOS, which includes estrogen resistance, leptin receptor insufficiency, folate deficiency, T2DM, and acanthosis nigricans, with obesity being a common phenotypic expression.

In sum, there is strong evidence that GBMs acquire novel mutations to survive outside the CNS. In some cases, tumor cells likely mutate after seeding scalp tissue during surgery, and in others, they mutate and spread without surgery. Future studies and genetic profiling of primary and metastatic lesions may help uncover the mechanisms of spread.

Additional mutations detected in the tumor included TP53, PTEN, and a PTPRZ1-MET fusion. This represents the first reported case of a CHEK2 germline mutation in giant cell glioblastoma, further supporting the significance of impaired DNA repair mechanisms in the development of this disease.

We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset.

We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.

Here we present a case series of metastatic LCNEC in which favorable clinical courses with persistent response periods towards immunochemotherapy with nivolumab/ipilimumab/carboplatin and paclitaxel were achieved. The case series presented here underlines the feasibility and efficacy of combined ICI targeting PD-1 and CTLA-4 in combination with a platinum doublet in metastatic LCNEC. Despite the limited number of cases, we suggest the TMB to be a frequent and potentially characteristic marker in LCNEC that is well known to predict responsiveness towards immunochemotherapy.

Ascl1 loss in established NEPC causes transient regression followed by recurrence, but its deletion before transplantation abrogates lineage plasticity, resulting in castration-sensitive adenocarcinomas. This dynamic model highlights the importance of therapy timing and offers a platform to identify additional lineage plasticity drivers.

This review underscores a multimodal diagnostic approach, merging molecular diagnostics with cytopathology, as a cornerstone in managing PCa effectively. This strategy promises a future where treatment is not only tailored to the individual's genetic makeup but also anticipates the disease's trajectory, offering hope for improved prognosis and quality of life for patients.

To advance our understanding of the role of breast cancer driver genes' mutational status with pathological complete response (pCR; ypT0/isypN0) prediction and to identify distinct gene sets for MTIs like eribulin and paclitaxel, we carried out targeted genomic (n = 50) and whole transcriptomic profiling (n = 64) of TNBC tumor samples from the Japan Breast Cancer Research Group 22 (JBCRG-22) clinical trial. Differential enrichment analysis of the HRD-high group posttreatment tumors revealed significant correlation (p = 0.006) of the glycan degradation pathway. FGFR2 expression and the differentially enriched pathways play a role in the response and resistance to MTIs containing carboplatin treatment in TNBC patients.

Our analysis demonstrated the prognostic significance of DAXX mutations after curative-intent surgery. Future studies investigating DAXX mutations as a biomarker for aggressive features to guide treatment are warranted.

Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.

Ipatasertib+paclitaxel demonstrated more encouraging activity. The tolerability of both regimens was consistent with previous experience.

When analyzing pioneer transcription factors, the AMPC lesion exhibited elevated FOXA1 activity while the brain NEPC lesion showed elevated HOXC10, NFYB, and OTX2 expression suggesting novel roles in NEPC formation or brain tropism. Our results highlight the utility of performing multi-omic characterization, especially in rare cancer subtypes.

CtDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management.

Epigenetic modifications, encompassing DNA methylation and microRNA dysregulation, further elucidate the molecular landscape. This review consolidates a comprehensive understanding of the molecular drivers of eyelid SGC, shedding light on potential therapeutic targets and providing a foundation for future investigations in diagnostic, prognostic, and personalized treatment strategies for this formidable malignancy.

This review summarizes the current knowledge and future perspectives of liquid biopsy of blood and CSF for diagnosis and monitoring of primary CNS tumors.

A novel finding was the discovery of an HMGA2::LINC02389 fusion in 1 patient with EMC ex-PA. The present results indicate that molecular profiling of CXPA with myoepithelial differentiation (MC) tends to reveal chromosomal fusion events, whereas CXPA with epithelial differentiation (SDC) tends to have a higher frequency of pathogenic mutations and gene amplifications.

The unique genomic landscape of PHTS-associated thyroid tumors carries implications for molecular-targeted therapies for patients. Exome sequencing reveals the distinct mutational landscape of PTEN hamartoma tumor syndrome-associated thyroid cancers from sporadic counterparts, providing insights into tumor progression and behavior that could help improve diagnosis, surveillance, and treatment.

P2, N=80, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial primary completion date: Sep 2026 --> Aug 2027

Our analysis uncovers synthetically lethal associations between the tumor metabolic state (e.g., oxidative phosphorylation), driver mutations (e.g., loss of tumor suppressor PTEN), and actionable biological targets (e.g., mitochondrial electron transport chain). Investigating the mechanisms underlying these relationships can inform the development of more precise and context-specific, metabolism-targeted cancer therapies.

Previously considered undruggable, sotorasib and adagrasib are the first available OFF-state KRASG12C inhibitors, but treatment resistance is frequent. We highlight the lack of data on non-genomic resistance and the need for comprehensive clinical studies exploring histological, genomic, and non-genomic changes at resistance. This knowledge could help foster new treatment initiatives in this challenging context.

WES revealed significant somatic and germline DNA mutations, with key pathogenic variants identified in genes such as PTEN, PIK3CA, TP53, MLH1, and MSH2. Comparative analysis showed distinct and overlapping mutation profiles, highlighting the importance of integrating somatic and germline data in endometrial cancer research.

P2, N=100, Recruiting, Nationwide Children's Hospital | Not yet recruiting --> Recruiting

P2, N=36, Completed, OHSU Knight Cancer Institute | Active, not recruiting --> Completed

Somatic NF1 mutations and co-mutations can play a critical driving force in metastatic lung adenocarcinoma and may contribute to treatment resistance. The mutational landscape of somatic NF1 mutations and co-mutations can provide new insights into the pathophysiology of metastatic lung cancer, especially those that have metastasized to the brain.

The addition of the rituximab further deepened the durability of capivasertib and venetoclax responses in a RCHOP refractory DLBCL in vivo models. These findings provide preclinical evidence for the rational treatment combination of AKT and BCL-2 inhibitors using capivasertib and venetoclax respectively alongside anti-CD20 antibody supplementation for treatment of patients with DLBCL.

P2, N=124, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Oct 2024 --> Jan 2028 | Trial primary completion date: Oct 2024 --> Jan 2026

KRAS is an attractive therapeutic strategy due to its high prevalence and its role in initiating and sustaining tumour growth. Approval of KRAS G12C inhibitors in locally advanced or metastatic NSCLC has brought hope to many patients. Studies show that non G12C KRAS mutation are found in 53% of adenocarcinomas.

Oncogenic activation of genes-drivers are responsible for resistance mechanisms either understood has resistance to METtargeted therapies and as primary resistance. Recently it has been reported that PI3K pathway alteration is common in concomitancy with METex14 and believed that confers primary resistance to MET TKI. Early identification of alterations in MET kinase domain at diagnosis, is crucial for understanding progression and resistance mechanism, to develop novel therapies or to design treatment strategies in order to improve patient outcomes.

Due to the majority of cases in our study being constituted of triple-negative cases, TP53 mutation, which is reported to be more common in these cases in the literature, was observed frequently. Most of the mutations we detected in our study have been reported to be associated with prognostic, predictive, and drug resistance implications, making their identification in breast tumours significant.

This study provides a comprehensive view of clinicopathological and genetic prognostic factors across different cancer types and draws attention to less commonly known factors which might help produce more precise prognosis and survival estimates. The results from this study contribute to the understanding of cancer disease and could be used by researchers to develop complex prognostic models, which in turn could help predict cancer prognosis more accurately and improve patient outcomes.

An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients.

Primary cytoreductive surgery with resection of all macroscopic detectable lesions should be performed whenever possible. More prospective, multicenter, large-scale trials are required to examine the regimens and therapeutic value of adjuvant chemotherapy or radiology.

Morphologic and molecular changes in EC recurrences, especially dedifferentiation and the acquisition of MMRd, should be considered for a correct diagnosis and treatment. MMRd should be tested in metastatic lesions, if available, in patients with primary tumors reported to be of a molecular subtype different from MMRd.