CDK4 amplification

Notably, the PNC phenotype relies on the expression of EBF3, an early neurogenic transcription factor, which is directly controlled by MYC transcription factors in accessible chromatin sites. Overall our findings indicate that the concomitant presence of genetic alterations, impinging on both cell cycle and p53 pathway control, strongly predisposes GBM to develop a concomitant poorly differentiated primitive phenotype depending on MYC-driven EBF3 transcription in a subset of glioma stem-like progenitor cells.

In contrast, higher-grade gliomas evade IFN signaling through genetic deletions of IFN gene clusters. These findings emphasize a broader epigenetic-to-genetic shift in oncogenic regulation that drives glioma progression, provides a valuable framework for understanding the transition from indolent tumors to lethal malignancies, and has implications for therapy and clinical management.

We identified two intimal sarcoma molecular subtypes. Compared with CNV-H, MSI-H-like is enriched in pathways associated with tumor immune responses and TILs. Further efforts and clinical trials to better define these molecular subtypes are warranted to open new avenues for personalized treatment approaches and improve patient outcomes.

In summary, ENTs arising from GCTs are molecularly heterogeneous; however, a large fraction of testicular ENTs could be stratified by two distinct sets of genetic alterations, including MYCN/MYC amplification with concurrent suppression of the p53 pathway, and activation of the PI3K pathway with co-occurring CDK4 amplification. Moreover, the novel gene fusions identified in a subset of testicular GCT-derived ENTs overlap with molecularly defined tumors of embryonic-type neuroectodermal features in the central nervous system, indicating the potential common driving events for tumorigenesis from different anatomic sites.

P1/2, N=30, Completed, Yonsei University | Active, not recruiting --> Completed

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.

Morphological diagnosis alone can accurately diagnose lipomas. However, it has a propensity to overdiagnose ALT/WDLPS. Thus, MDM2 FISH should be used more proactively, not only for lesions with obvious morphological abnormalities, but also for lipomatous tumors that are clinically suggestive of ALT/WDLPS.

P2, N=45, Recruiting, Massachusetts General Hospital | N=30 --> 45 | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

Furthermore, it is observed that this co-delivery system can activate immune microenvironment, increasing CD8+ T cell infiltration and converting osteosarcoma from an immune-cold to an immune-hot tumor. In summary, the co-delivery system is an effective therapeutic strategy and holds promise as a novel approach for osteosarcoma treatment.

No recurrence was observed during the follow-up period of 8 months. This study aims to improve our understanding of PF by analyzing the clinicopathological characteristics of this case, including immunohistochemical (IHC) and genetic examination, and reviewing relevant literature.

We reviewed demographic data, treatment histories, and overall response rates (ORR). We identified five patients with DDLPS who were treated with CDK4/6i, palbociclib and abemaciclib. In untreated WD/DD LPS, baseline alterations in cyclin D are rare. Our analysis revealed that three patients with DDLPS acquired either cyclin D1 or cyclin D2 amplification in progressing samples following treatment with CDK4/6i. Unlike breast cancer, where cyclin E1 amplification is a well-established driver of resistance to CDK4/6i, these findings suggest a potential role for cyclin D amplification in acquired resistance in LPS.

This study demonstrates that immunohistochemistry for MDM2 and CDK4 can help elucidate the molecular genetic features of UA. Further studies are needed to correlate the expression of these genes with the biological behavior of UA.