Fengerscarborough9594

Methylated cytosines deaminate at higher rates than unmethylated cytosines and the lesions they produce are repaired less efficiently. As a result, methylated cytosines are mutational hotspots. Here, combining rare polymorphism and base-resolution methylation data in human, Arabidopsis thaliana, and rice (Oryza sativa), we present evidence that methylation state affects mutation dynamics not only at the focal cytosine but also at neighbouring nucleotides. In human, contrary to prior suggestions, we find that nucleotides in the close vicinity (±3bp) of methylated cytosines mutate less frequently. Reduced mutability around methylated CpGs is also observed in cancer genomes, considering single nucleotide variants alongside tissue-of-origin-matched methylation data. In contrast, methylation is associated with increased neighbourhood mutation risk in A. thaliana and rice. The difference in neighbourhood mutation risk is less pronounced further away from the focal CpG and modulated by regional GC content. Our results are consistent with a model where altered risk at neighbouring bases is linked to lesion formation at the focal CpG and subsequent long-patch repair. selleck chemical Our findings indicate that cytosine methylation has a broader mutational footprint than is commonly assumed. Copyright © 2020, Genetics.Previously unidentified breast cancer subtypes that may be linked to prognosis were identified using imaging mass cytometry, a recently invented and rapidly developing technique that allows spatial relationships among cells expressing selected markers to be determined. ©2020 American Association for Cancer Research.PURPOSE To (i) create a survival risk score using radiomic features from the tumor habitat on routine MRI to predict progression-free survival (PFS) in glioblastoma and (ii) obtain a biological basis for these prognostic radiomic features, by studying their radiogenomic associations with molecular signaling pathways. EXPERIMENTAL DESIGN Two hundred three patients with pretreatment Gd-T1w, T2w, T2w-FLAIR MRI were obtained from 3 cohorts The Cancer Imaging Archive (TCIA; n = 130), Ivy GAP (n = 32), and Cleveland Clinic (n = 41). Gene-expression profiles of corresponding patients were obtained for TCIA cohort. For every study, following expert segmentation of tumor subcompartments (necrotic core, enhancing tumor, peritumoral edema), 936 3D radiomic features were extracted from each subcompartment across all MRI protocols. Using Cox regression model, radiomic risk score (RRS) was developed for every protocol to predict PFS on the training cohort (n = 130) and evaluated on the holdout cohort (n = 73). Further, Gene Ontology and single-sample gene set enrichment analysis were used to identify specific molecular signaling pathway networks associated with RRS features. RESULTS Twenty-five radiomic features from the tumor habitat yielded the RRS. A combination of RRS with clinical (age and gender) and molecular features (MGMT and IDH status) resulted in a concordance index of 0.81 (P less then 0.0001) on training and 0.84 (P = 0.03) on the test set. Radiogenomic analysis revealed associations of RRS features with signaling pathways for cell differentiation, cell adhesion, and angiogenesis, which contribute to chemoresistance in GBM. CONCLUSIONS Our findings suggest that prognostic radiomic features from routine Gd-T1w MRI may also be significantly associated with key biological processes that affect response to chemotherapy in GBM. ©2020 American Association for Cancer Research.Hepatosplenic space occupying lesions are usually labelled as metastasis. This case highlights the importance of thinking beyond malignancy and the importance of adopting a systematic approach when dealing with such lesions that have a plethora of close differentials. Hepatosplenic tuberculosis is a rare form of extra pulmonary tuberculosis. Timely diagnosis and treatment turned the table from a probable dismal prognosis to a completely curable cause. We report an unusual case, which was provisionally labelled as malignancy, due to isolated liver and spleen involvement but on evaluation turned out to be tuberculosis. The patient got cured with 6 months of anti-tubercular therapy. The report also brings to light the possible use of molecular methods like cartridge-based nucleic acid amplification test in diagnosing hepatobiliary tuberculosis, the literature about which is very scarce and limited. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Winged scapula is a rare condition caused by injuries to the long thoracic nerve (LTN) and accessory nerves. A 69-year-old man underwent surgery for right lung cancer. Video-assisted thoracic surgery was converted to axillary thoracotomy at the fourth intercostal space. The latissimus dorsi was protected, and the serratus anterior was divided on the side anterior to the LTN. Two months after discharge, he presented with difficulty in elevating his right arm and protrusion of the scapula from his back. Active forward flexion of the right shoulder was limited to 110° and abduction to 130°. He was diagnosed with winged scapula. After 6 months of occupational therapy, the symptoms improved. The LTN may have been overstretched or damaged by the electric scalpel. We recommend an increased awareness of the LTN, and to divide the serratus anterior at a site as far as possible from the LTN to avoid postoperative winged scapula. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.Giant cell tumour of the tendon sheath (GCTTS) commonly presents as a slow-growing and painless soft-tissue lesion in the hand. It has a propensity to mimick other benign and malignant lesions of the hand including lipoma, haemangioma, myxoid cyst, synovial sarcoma, aneurysmal bone cyst, fibroma and osteosarcoma. GCTTS has a unique histopathological appearance that aids in definitive diagnosis. Although bony invasion and local aggressive characteristics have only been reported rarely, the treatment of choice is local excision. The following case illustrates a fairly typical presentation of GCTTS with certain atypical features. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.