Search

Ependymomas encompass multiple, clinically relevant tumor types based on localization, genetic alterations, and epigenetic and transcriptomic profiles. Tumors belonging to the methylation class of spinal ependymoma (SP-EPN) represent the most common intramedullary neoplasms in children and adults. However, molecular data of SP-EPN are scarce, and clear treatment recommendations are lacking. The only known recurrent genetic events in SP-EPN are loss of chromosome 22q and NF2 mutations. Yet, it remains unclear whether SP-EPN with germline or sporadic NF2 mutations or with NF2 wild type status differ clinically or molecularly. To provide a comprehensive molecular profile of SP-EPN, we integrated epigenetic, genomic, transcriptomic, and histological analyses of up to 237 cases. Clustering of methylation data revealed two distinct molecular SP-EPN subtypes. The distribution of NF2 mutated cases differed significantly across these subtypes (p

DNA methylation profiling led to the definition of ten molecular types of ependymomas with distinct biological and clinical features. The largest published reference cohort consists of 500 ependymomas encompassing nine molecular types that were known at this point. Our study aimed to confirm and refine molecular and clinical characteristics of ependymoma types and subtypes based on a considerably larger, well-annotated cohort of ependymal tumors. Here, we analyzed previously published and newly generated DNA methylation profiles, generated on the Illumina 450k and EPIC arrays, from a total of n=1,801 ependymomas. We looked at both global DNA methylation as well as inferred copy number profiles and correlated these data with clinical parameters. Patients with EPN-PFA, EPN-RELA, and EPN-MYCN tumors showed the worst outcome with 10 year-overall survival rates of 56%, 64%, and a 5 year-overall survival rate of 73%, respectively. EPN-PFA, the most frequent tumor type in our series, occurred in children in >98% of cases, epigenetically split into two major subtypes, and harbored chromosome 1q gains and 6q losses as markers for worse survival (p

Myxopapillary ependymoma (MPE) is a heterogeneous disease regarding histopathology and outcome. The underlying molecular biology is poorly understood, and markers that reliably predict the patients’ clinical course are unknown. We assembled a cohort of 185 tumors classified as MPE based on DNA methylation from pediatric, adolescent, and adult patients. Methylation patterns, copy number profiles, and MGMT promoter methylation were analyzed for all tumors, 106 tumors were evaluated histomorphologically, and RNA sequencing was performed for 37 cases. Based on methylation profiling, we defined two subtypes MPE-A and MPEB, and explored associations with epidemiological, clinical, pathological, and molecular characteristics of these tumors. Tumors in the methylation class MPE were histologically diagnosed as WHO grade I (59%), WHO grade II (37%), or WHO grade III tumors (4%). 75/77 analyzed tumors expressed HOXB13, which is a diagnostic feature not detected in other spinal ependymal tumors. Based on DNA methylation, our series split into two subtypes. MPE-A occurred in younger patients (median age 27 vs. 45 years, p=7.3e-05). They were enriched with WHO grade I tumors and associated with papillary morphology and MGMT promoter hypermethylation (all p

Pancreatic ductal carcinoma (PDAC) is a highly lethal cancer, and early detection and accurate staging are critical to prolonging survival. PDAC typically has a prominent stroma including cancer-associated fibroblasts that express fibroblast activation protein (FAP). FAP is a new target molecule for PET imaging of various tumors. In this retrospective study, we describe the clinical impact of PET/CT imaging using (68)Ga-labeled FAP-inhibitors ((68)Ga-FAPI PET/CT) in 19 patients with PDAC (7 primary, 12 progressive/recurrent). Methods: All patients underwent contrast-enhanced CT (ceCT) for TNM staging before (68)Ga-FAPI PET/CT imaging. PET scans were acquired 60 min after administration of 150–250 MBq of (68)Ga-labeled FAP-specific tracers. To characterize (68)Ga-FAPI uptake over time, additional scans after 10 or 180 min were acquired in 6 patients. SUV(max) and SUV(mean) values of PDAC manifestations and healthy organs were analyzed. The tumor burden according to (68)Ga-FAPI PET/CT was compared with TNM staging based on ceCT and changes in oncologic management were recorded. Results: Compared with ceCT, (68)Ga-FAPI PET/CT results led to changes in TNM staging in 10 of 19 patients. Eight of 12 patients with recurrent/progressive disease were upstaged, 1 was downstaged, and 3 had no change. In newly diagnosed PDAC, 1 of 7 patients was upstaged, and the staging of 6 patients did not change. Changes in oncologic management occurred in 7 patients. Markedly elevated uptake of (68)Ga-FAPI in PDAC manifestations after 1 h was seen in most cases. Differentiation from pancreatitis based on static imaging 1 h after injection was challenging. With respect to imaging after multiple time points, PDAC and pancreatitis showed a trend for differential uptake kinetics. Conclusion: (68)Ga-FAPI PET/CT led to restaging in half of the patients with PDAC and most patients with recurrent disease compared with standard of care imaging. The clinical value of (68)Ga-FAPI PET/CT should be further investigated.