33 research outputs found
Erratum to: Clinical metagenomic identification of Balamuthia mandrillaris encephalitis and assembly of the draft genome: the continuing case for reference genome sequencing
Genetic and epigenetic characterization of posterior pituitary tumors
Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets
The effect of ω-fatty acids on mrna expression level of PPARγ in patients with gastric adenocarcinoma
Background: The antineoplastic role of peroxisome proliferator-activated receptor gamma (PPARγ) ligandshas previously been demonstrated in several gastric cancer cell lines. Activation of PPARγ by polyunsaturated fatty acids (PUFAs) inhibits growth and proliferationof tumor cells. In this double-blind clinical study, we evaluate the effect of PUFAs on PPARγ mRNA expression in patients with gastric adenocarcinoma. Materials and Methods: A total of 34 chemotherapy-naive patients diagnosed with gastric adenocarcinoma were enrolled in the present study. According to treatment strategies, all subjects were divided into two groups, the first group (17 individuals) received cisplatin without supplements and the second group (17 individuals) received cisplatin plus orally administered PUFAs supplements for 3 weeks. The gastric biopsy samples were obtained from all participants before and after treatment, and PPARγ mRNA expression levels were evaluated by quantitative real-time polymerase chain reaction using validated reference genes. Results: Our findings revealed that PPARγ mRNA expression is significantly upregulated in group II afterreceiving cisplatin plus orally administered PUFAs supplements for three weeks (p < 0.0001), whereas PPARγ mRNA expression did not show significant alteration in group I after receiving cisplatin alone. Conclusion: The results of the study evidence that PPARγ may act as a potential target for the therapy of human gastric adenocarcinoma
Clinical metagenomic identification of Balamuthia mandrillaris encephalitis and assembly of the draft genome: the continuing case for reference genome sequencing
Recommended from our members
IgG4 in Inflammation‐Rich Meningioma
Meningiomas with prominent inflammation are traditionally classified as "lymphoplasmacyte-rich meningioma" (LPM). Both inflammatory and neoplastic meningeal proliferations have recently been linked to IgG4 disease, although a potential association with LPM has not been previously explored. Sixteen meningiomas with inflammatory cells outnumbering tumor cells were further characterized by CD3, CD20, CD68 and/or CD163, CD138, kappa, lambda, IgG and IgG4 immunostains. There were 11 female and 4 male patients, ranging from 22 to 78 (median 59) years of age. Tumors consisted of 10 World Health Organization (WHO) grade I, 5 grade II and 1 grade III LPMs. Immunohistochemically, the most numerous cell type was the macrophage in all cases followed by CD3-positive T cells and fewer CD20-positive B cells. Plasma cells ranged from moderate-marked (N = 5) to rare (N = 7), or absent (N = 4). Maximal numbers of IgG4 plasma cells per high power field (HPF) ranged from 0 to 32, with only two cases having counts exceeding 10/HPF. The IgG4/IgG ratio was increased focally in only two cases (30% and 31%). Additionally, plasma cells represented only a minor component in most examples, whereas macrophages predominated, suggesting that "inflammation-rich meningioma" may be a more accurate term. The inflammatory stimulus for most cases remains to be elucidated