Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study.

Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1-3 arose in older children (median ages 5.2-14.0 years) and had intermediate to excellent survival (5-year OS of 68.0-100%), while Group RB and MYC PB patients were much younger (median age 1.3-1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age < 3 years at diagnosis, metastatic disease, omission of upfront radiation, and chr 16q loss as significant negative prognostic factors across all PBs. Our findings demonstrate that PB exhibits substantial molecular heterogeneity with sub-group-associated clinical phenotypes and survival. In addition to revealing novel biology and therapeutics, molecular sub-grouping of PB can be exploited to reduce treatment intensity for patients with favorable biology tumors

Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: a Rare Brain Tumor Consortium registry study

Pineoblastomas (PBs) are rare, aggressive pediatric brain tumors of the pineal gland with modest overall survival despite intensive therapy. We sought to define the clinical and molecular spectra of PB to inform new treatment approaches for this orphan cancer. Tumor, blood, and clinical data from 91 patients with PB or supratentorial primitive neuroectodermal tumor (sPNETs/CNS-PNETs), and 2 pineal parenchymal tumors of intermediate differentiation (PPTIDs) were collected from 29 centres in the Rare Brain Tumor Consortium. We used global DNA methylation profiling to define a core group of PB from 72/93 cases, which were delineated into five molecular sub-groups. Copy number, whole exome and targeted sequencing, and miRNA expression analyses were used to evaluate the clinico-pathologic significance of each sub-group. Tumors designated as group 1 and 2 almost exclusively exhibited deleterious homozygous loss-of-function alterations in miRNA biogenesis genes (DICER1, DROSHA, and DGCR8) in 62 and 100% of group 1 and 2 tumors, respectively. Recurrent alterations of the oncogenic MYC-miR-17/92-RB1 pathway were observed in the RB and MYC sub-group, respectively, characterized by RB1 loss with gain of miR-17/92, and recurrent gain or amplification of MYC. PB sub-groups exhibited distinct clinical features: group 1–3 arose in older children (median ages 5.2–14.0 years) and had intermediate to excellent survival (5-year OS of 68.0–100%), while Group RB and MYC PB patients were much younger (median age 1.3–1.4 years) with dismal survival (5-year OS 37.5% and 28.6%, respectively). We identified age

Position specific isotope analysis: the ultimate tool in environmental forensics?

Here we propose a 'leap foward' with the application of Position Specific Isotope Analysis to Environmental Forensics, a topic which has a large un-tapped potential for biogeochemical / biodegradation studies. Compound specific isotope analysis (CSIA) is a relatively new methods in Enviornmental Forenscis (figuring out where the contamination in the environment comes from). PSIA could uncover / unlock the questions that CSIA has opened up and leap-frog our understanding of the fate of contaminants in the environment. Isotopic fractionation is limited to reactions at the site or bond in the contaminant molecule associated with the rate-limiting biodegradation step. These fractionation effects are diluted in 'whole molecule' CSIA by the presence of non-reacting carbon atoms. Intramolecular isotope ratios however would be sensitive to such fractionation effects and could be used to determine the pathways and mechanism of degradation. Leveraging the resources of Prof. Kalin's EPSRC funded Platform Grant therefore provides the 'base-line real-world' access to sites and samples for this proposed 'Speculative Engineering' research, thereby allowing the research proposed here to solely focus on solving the question: Is PSIA useful for Environmental Forensics applications?Current convention would say that PSIA is impracticable for the 'real world', however we challenge this and firmly believe in the potential of this approach. There are many other areas of research that may benefit from a concerted speculative research effort on the Environmental Forensic application of PSIA, the results of which are certain to give some insight into the biogeochemical cycling of contaminant organic compounds released to the environment

Sclerosing nodular lesions of the gastrointestinal tract containing large numbers of IgG4 plasma cells

Background: Hyalinised fibrous nodules have been encountered within the gastrointestinal tract (GIT) and been labelled as reactive nodular fibrous tumours. Several have a history of abdominal surgery and/or sepsis that acts as a precipitating cause for the fibrosis. Recently, much attention has been focused on IgG4 related fibrosing lesions that are typically associated with a high population of IgG4 positive plasma cells and tissue fibrosis. There may be attendant elevated serum IgG4 levels and associated autoimmune disease. Methods: We present four patients with well-circumscribed fibrous nodular lesions occurring in the GIT. Tissue was formalin fixed after microwave antigen retrieval and H&amp;E stains and immunohistochemistry were performed. IgG4/IgG ratios were calculated from the three high power fields containing the densest concentration of positive plasma cells. Results: The patients were two females (45 and 56 years) and two males (47 and 60 years) who presented with gastric (2 cases), caecal and sigmoid flexure involvement. One case had four lesions while the other three cases were solitary nodules. Two patients had coexistent autoimmune disease. All lesions were nodular and composed of paucicellular, hyalinised fibrous tissue associated with chronic inflammation. In all lesions the plasma cell population was strongly IgG4 positive. Conclusions: This paper describes unique, well-circumscribed sclerosing nodules containing IgG4 positive plasma cells within the bowel wall that may cause mucosal polypoid lesions. It is possible that these lesions may be related to the spectrum of IgG4 related sclerosing disease or belong to a separate subset of inflammatory reactive conditions that are rich in IgG4 plasma cells

Bioaugmentation reduces negative effect of estrogens on coliform removal in slow sand filters

No abstract available

Bioaugmentation reduces negative effect of estrogens on coliform removal in slow sand filters

No abstract available

Zosteriform configuration of multiple eccrine spiradenomas of the scalp

International audienceBACKGROUND:Eccrine spiradenoma (ES) is a benign adnexal tumor predominantly located in the head and neck regions. Multiple neoplasms located on the scalp have been reported but never with a zosteriform configuration on the first trigeminal area.CASE REPORT:We describe an original case report of a 75-year-old Caucasian man presenting multiple subcutaneous blue and purple nodules disseminated on the first left trigeminal dermatome. All the nodules appeared gradually on a one-year period. Biopsy revealed a nodular adnexal tumor in the dermis without malignant eccrine spiradenoma (MES) transformation. The surgical procedure was performed in a manner to protect the galea aponeurotica in the upper half on the first left trigeminal area. The frontalis muscle was raised with the surgical specimen in the lower half of the first trigeminal area. A split-thickness skin graft was applied on the surgical defect. Histological examination revealed multilobular well-defined tumors located in the dermis.CONCLUSION:The presence of multiple subcutaneous nodules in a trigeminal pattern should suggest a multiple localized zosteriform ES. The diagnosis is focused on clinical findings and the treatment is based on a large surgical excision. The histological examination is essential for not to fail a MES transformation

Fingerprinting polychlorinated biphenyls in environmental samples using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry

A GC × GC-TOFMS installed with a Rtx-PCB (60 m × 0.18 mm × 0.18 μm) in the first dimension and Rxi- 17 (1.5 m × 0.1 mm × 0.1 μm) column in the second dimension was used to separate 188 out of 209 congeners. A further 12 congeners were identified through additional data processing resulting in the identification of a total of 200 congeners. However, caution is advised if these 12 congeners were to be used in quantitative assessments. The remaining 9 co-eluting congeners were three doublets (CB65 + CB62, CB160 + CB163 and CB201 + CB204) and one triplet (CB20 + CB21 + CB33). This method was tested on five Aroclors and resulted in the separation of all congeners present in the heavier Aroclor mixtures A1254 and A1260. The suitability of this method for applications in biological matrices was demonstrated on extracted whiting and guillemot liver samples which resulted in the identification of 137 individual PCBs in the whiting liver sample and 120 in the guillemot sample. Fingerprinting was able to show clear differences in the PCB signature of the two animals. This highlights the potential of this method for PCB fingerprinting in environmental forensics studies and other assessments that require congener specific analysis