ATRX deletion

The T2/FLAIR mismatch sign detected diffuse astrocytomas with 100% specificity. When combined with high Cho/Cr and raised rCBV, this predicted histological grading with high accuracy. The future direction for imaging should explore a similar integrated layered approach of 2021 classification of central nervous system (CNS) tumours combining radio-phenotyping and grading from structural and multiparametric imaging.

Conclusions Deep learning can detect ALT cancers from targeted sequencing data across various cancer types. This new method enables the dissection of genomic and phenotypic characteristics of ALT cancers in large retrospective cohorts with available targeted sequencing data, while providing a potentially high-throughput, accessible means to enroll patients in prospective studies targeting the ALT phenotype.

We found that both human and mouse models of Atrx deleted sarcoma had a reduced adaptive immune response, markedly impaired CGAS/STING signaling, and increased sensitivity to TVEC, an oncolytic herpesvirus that is currently FDA approved for the treatment of aggressive melanomas. Translation of these results to patients with ATRX mutant cancers could enable genomically-guided cancer therapeutic approaches that improve patient outcomes.

In a prospective, multicenter, international testing cohort of patients with diffuse glioma (n = 153) who underwent real-time SRH imaging, we demonstrate that DeepGlioma can predict the molecular alterations used by the World Health Organization to define the adult-type diffuse glioma taxonomy (IDH mutation, 1p19q co-deletion and ATRX mutation), achieving a mean molecular classification accuracy of 93.3 ± 1.6%. Our results represent how artificial intelligence and optical histology can be used to provide a rapid and scalable adjunct to wet lab methods for the molecular screening of patients with diffuse glioma.

These findings provide a strong rationale for clinically evaluating B7-H3-CAR T for pediatric patients with chemotherapy-resistant ACC. Additionally, the newly established pediatric ACC PDX models provide a valuable resource for investigating different aspects of this rare and aggressive disease.

Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.

Notably, out of 196 mesenchymal neoplasms of gynecologic origin, BAP1 homozygous deletion was only found in adenosarcomas (P = 0.0003). This study demonstrates that high-grade adenosarcomas are heterogeneous at the molecular level and are characterized by genomic instability and TP53 mutations; ATRX loss may be involved in high-grade transformation of low-grade adenosarcoma; and BAP1 inactivation appears to be a specific pathogenic driver in a subset of adenosarcomas.

Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.

To generate the first primary mouse model of soft tissue sarcoma, 4-hydroxytamoxifen (4-OHT) was injected into the gastrocnemius muscle... Collectively, these results show that loss of ATRX function impairs the cGAS-STING signaling pathway in soft tissue sarcomas and promotes their response to radiation therapy and oncolytic virus therapy. These findings identify ATRX as a biomarker in treatment response and identify novel genomically-informed therapeutic strategies for treatment of soft tissue sarcoma.

Based on IHC and genetic analyses of the biopsied samples, three patients were enrolled into the Phase 0/2 clinical trial and baseline value were used for PD analysis. CONCLUSION Single-pass stereotactic needle biopsy is a feasible and safe strategy to collect pre-treatment tissue in support of a Phase 0 clinical trial, enabling CLIA-certified genetic analysis for trial screening and tumor PD analysis.

DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.