Delineation of human prostate cancer evolution identifies chromothripsis as a polyclonal event and FKBP4 as a potential driver of castration resistance
Abstract
Understanding the evolutionary mechanisms and genomic events leading to castration resistant (CR) prostate cancer (PC) is key to improve the outcome of this otherwise deadly disease. Here, we delineated the tumour history of seven patients progressing to castration resistance by analysing matched prostate cancer tissues before and after castration. We performed genomic profiling of DNA‐content based flow‐sorted populations in order to define the different evolutionary patterns. In one patient, we discovered that a catastrophic genomic event, known as chromothripsis, resulted in multiple CRPC tumour populations...
Source: The Journal of Pathology - February 27, 2018 Category: Pathology Authors: Jo ël R. Federer‐Gsponer, Cristina Quintavalle, David C. Müller, Tanja Dietsche, Valeria Perrina, Thomas Lorber, Darius Juskevicius, Elisabeth Lenkiewicz, Tobias Zellweger, Thomas Gasser, Michael T. Barrett, Cyrill A. Rentsch, Lukas Bubendorf, Christi Tags: Original Paper Source Type: research
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The Journal of Pathology, Ahead of Print. (Source: The Journal of Pathology)
Source: The Journal of Pathology - February 26, 2018 Category: Pathology Source Type: research
Breaking the Oncostatin M feed ‐forward loop to suppress metastasis and therapy failure
ABSTRACT
Deciphering the complex milieu that makes up the tumor microenvironment (TME) and the signaling engaged by TME cytokines continues to provide novel targets for therapeutic intervention. The IL‐6 family member Oncostatin M (OSM) has recently emerged as a potent driver of tumorigenesis, metastasis and therapy failure, molecular programs most frequently attributed to IL‐6 itself. In a recent issue of The Journal of Pathology, Kucia‐Tran et al. describe how elevated Oncostatin M receptor (OSMR) expression results in a feed‐forward loop involving the de novo production of both OSM and OSMR to facilitate aggress...
Source: The Journal of Pathology - February 23, 2018 Category: Pathology Authors: Jacob Smigiel, Jenny G. Parvani, Ilaria Tamagno, Kelsey Polak, Mark W. Jackson Tags: Invited Commentary Source Type: research
Capillary morphogenesis protein 2 is a novel prognostic biomarker and plays oncogenic roles in glioma
Abstract
Capillary morphogenesis protein 2 (CMG2) was originally identified through its participation in capillary morphogenesis, and subsequently identified as the second receptor for anthrax toxin (ANTXR2). Although tumor‐associated functions of CMG2 have also been reported, the clinical significance and functional mechanism of CMG2 in glioma remain to be elucidated. We assessed the clinicopathological relevance of CMG2 in a cohort of 48 glioma patients as well as through public glioma databases, and explored the function of CMG2 using glioblastoma (GBM) models in vitro and in vivo. CMG2 overexpression was associated w...
Source: The Journal of Pathology - February 23, 2018 Category: Pathology Authors: Juan Tan, Mei Liu, Jun ‐Ying Zhang, Yue‐Liang Yao, Yan‐Xia Wang, Yong Lin, Kang Song, Jiao Tan, Jin‐Rong Wu, You‐Hong Cui, Yan Wang, Xiu‐Wu Bian Tags: Original Paper Source Type: research
Proinflammatory role of blister fluid ‐derived exosomes in bullous pemphigoid
Abstract
Bullous pemphigoid is an autoimmune inflammatory disorder characterised by the presence of autoantibodies against bullous pemphigoid autoantigens, leading to dermal–epidermal separation with consequent blister formation. However, whether and how the components of blister fluid exacerbate the progression of bullous pemphigoid is unclear. Exosomes are nanometre‐sized vesicles released from cells into the body fluid, where they can transmit signals throughout the body. In the present study, we isolated and characterised exosomes from the blister fluids of patients with bullous pemphigoid, evaluated their proinfla...
Source: The Journal of Pathology - February 22, 2018 Category: Pathology Authors: Hui Fang, Shuai Shao, Man Jiang, Erle Dang, Shengxian Shen, Jieyu Zhang, Pei Qiao, Caixia Li, Gang Wang Tags: Original Paper Source Type: research
PanCancer insights from The Cancer Genome Atlas: the pathologist's perspective
Abstract
The Cancer Genome Atlas (TCGA) represents one of several international consortia dedicated to performing comprehensive genomic and epigenomic analyses of selected tumour types to advance our understanding of disease and provide an open‐access resource for worldwide cancer research. Thirty‐three tumour types (selected by histology or tissue of origin, to include both common and rare diseases), comprising >11 000 specimens, were subjected to DNA sequencing, copy number and methylation analysis, and transcriptomic, proteomic and histological evaluation. Each cancer type was analysed individually to identify ti...
Source: The Journal of Pathology - February 22, 2018 Category: Pathology Authors: Lee AD Cooper, Elizabeth G Demicco, Joel H Saltz, Reid T Powell, Arvind Rao, Alexander J Lazar Tags: Invited Review Source Type: research
Richter transformation driven by Epstein ‐Barr virus reactivation during therapy‐related immunosuppression in chronic lymphocytic leukemia
ABSTRACT
The increased risk of Richter transformation (RT) in patients with chronic lymphocytic leukemia (CLL) due to Epstein‐Barr virus (EBV) reactivation during immunosuppressive therapy with fludarabine or other targeted agents remains controversial. Among 31 RT cases classified as diffuse large B‐cell lymphoma (DLBCL), seven (23%) showed EBV expression. In comparison to EBV‐negative tumors, EBV+ DLBCLs derived predominantly from IGVH‐hypermutated CLL and exhibited CLL‐unrelated IGVH sequences more frequently. Intriguingly, despite having different cellular origins, clonally related and unrelated EBV+ DLBCLs s...
Source: The Journal of Pathology - February 21, 2018 Category: Pathology Authors: Maria J. Garc ía‐Barchino, Maria E Sarasquete, Carlos Panizo, Julie Morscio, Antonio Martinez, Miguel Alcoceba, Vicente Fresquet, Blanca Gonzalez‐Farre, Bruno Paiva, Ken H. Young, Eloy F. Robles, Sergio Roa, Jon Celay, Marta Larrayoz, Davide Rossi, G Tags: Original Paper Source Type: research
Translational control of aberrant stress responses as a hallmark of cancer
Abstract
Altered mRNA translational control is emerging as a critical factor in cancer development and progression. Targeting specific elements of the translational machinery, such as mTORC1 or eIF4E, is emerging as a new strategy for innovative cancer therapy. While translation of most mRNAs takes place through cap‐dependent mechanisms, a sub‐population of cellular mRNA species, particularly stress‐inducible mRNAs with highly structured 5'‐UTR regions, are primarily translated through cap‐independent mechanisms. Intriguingly, many of these mRNAs encode proteins that are involved in tumour cell adaptation to micr...
Source: The Journal of Pathology - February 20, 2018 Category: Pathology Authors: Amal M El ‐Naggar, Poul H Sorensen Tags: Invited Review Source Type: research
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The Journal of Pathology, Ahead of Print. (Source: The Journal of Pathology)
Source: The Journal of Pathology - February 16, 2018 Category: Pathology Source Type: research
Spatial Aspects of Oncogenic Signaling Determine Response to Combination Therapy in Slice Explants from Kras ‐driven Lung Tumors
ABSTRACT
A key question in precision medicine is how functional heterogeneity in solid tumors informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signaling and therapy response can be modeled in precision‐cut slices from Kras‐driven non‐small cell lung cancer (NSCLC) of varying histopathologies. Unexpectedly, profiling of in situ tumors demonstrates that signaling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma (ASC), and MAPK activity in adenocarcinoma (AC). In addition, high inter‐ and intra‐tumor variability i...
Source: The Journal of Pathology - February 15, 2018 Category: Pathology Authors: Katja N ärhi, Ashwini S. Nagaraj, Elina Parri, Riku Turkki, Petra W. van Duijn, Annabrita Hemmes, Jenni Lahtela, Virva Uotinen, Mikko I. Mäyränpää, Kaisa Salmenkivi, Jari Räsänen, Nina Linder, Jan Trapman, Antti Rannikko, Olli Kallioniemi, Taija af Tags: Original Paper Source Type: research
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The Journal of Pathology, Ahead of Print. (Source: The Journal of Pathology)
Source: The Journal of Pathology - February 14, 2018 Category: Pathology Source Type: research
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The Journal of Pathology,Volume 244, Issue 3, Page 255-256, March 2018. (Source: The Journal of Pathology)
Source: The Journal of Pathology - February 14, 2018 Category: Pathology Source Type: research
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The Journal of Pathology,Volume 244, Issue 3, Page 380-380, March 2018. (Source: The Journal of Pathology)
Source: The Journal of Pathology - February 14, 2018 Category: Pathology Source Type: research
Human papillomavirus genome integration in squamous carcinogenesis: what have next generation sequencing studies taught us?
Abstract
Human papillomavirus (HPV) infection is associated with ~5% of all human cancers, including a range of squamous cell carcinomas (SCCs). Persistent infection by high‐risk HPVs (HRHPVs) is associated with the integration of virus genomes (which are usually stably maintained as extrachromosomal episomes) into host chromosomes. Although HRHPV integration rates differ across human sites of infection, this process appears to be an integral event in HPV‐associated neoplastic progression, leading to deregulation of virus oncogene expression, host gene expression modulation and further genomic instability. However, the...
Source: The Journal of Pathology - February 14, 2018 Category: Pathology Authors: Ian J Groves, Nicholas Coleman Tags: Invited Review Source Type: research
