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https://www.readbyqxmd.com/read/28426098/targeting-chromatin-defects-in-selected-solid-tumors-based-on-oncogene-addiction-synthetic-lethality-and-epigenetic-antagonism
#1
D Morel, G Almouzni, J-C Soria, S Postel-Vinay
Background: Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28409567/sf3b1-and-bap1-mutations-in-blue-nevus-like-melanoma
#2
Klaus G Griewank, Hansgeorg Müller, Louise A Jackett, Michael Emberger, Inga Möller, Johannes Ap van de Nes, Lisa Zimmer, Elisabeth Livingstone, Thomas Wiesner, Simone L Scholz, Ioana Cosgarea, Antje Sucker, Tobias Schimming, Uwe Hillen, Bastian Schilling, Annette Paschen, Henning Reis, Thomas Mentzel, Heinz Kutzner, Arno Rütten, Rajmohan Murali, Richard A Scolyer, Dirk Schadendorf
Blue nevi are melanocytic tumors originating in the cutaneous dermis. Malignant tumors may arise in association with or resembling blue nevi, so called 'blue nevus-like melanoma', which can metastasize and result in patient death. Identifying which tumors will behave in a clinically aggressive manner can be challenging. Identifying genetic alterations in such tumors may assist in their diagnosis and prognostication. Blue nevi are known to be genetically related to uveal melanomas (eg, both harboring GNAQ and GNA11 mutations)...
April 14, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28408295/genomic-alterations-as-predictors-of-survival-among-patients-within-a-combined-cohort-with-clear-cell-renal-cell-carcinoma-undergoing-cytoreductive-nephrectomy
#3
Daniel M Tennenbaum, Brandon J Manley, Emily Zabor, Maria F Becerra, Maria I Carlo, Jozefina Casuscelli, Almedina Redzematovic, Nabeela Khan, Maria E Arcila, Martin H Voss, Darren R Feldman, Robert J Motzer, Nicole E Benfante, Jonathan A Coleman, Paul Russo, James J Hsieh, Abraham Ari Hakimi
PURPOSE: To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: We identified 60 patients who presented with metastatic ccRCC at our institution between 2001 and 2015 and had genomic sequencing on their primary tumor. We pooled these patients with 107 other patients with the same inclusion criteria from three well-known public databases. Five commonly mutated genes were chosen for analysis: VHL, PBRM1, BAP1, SETD2, and KDM5C...
April 10, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28404968/loss-of-nuclear-bap1-expression-is-associated-with-poor-prognosis-in-oral-mucosal-melanoma
#4
Hao Song, Lizhen Wang, Jiong Lyu, Yunteng Wu, Wei Guo, Guoxin Ren
Oral mucosal melanoma (OMM) is an aggressive neoplasm with an extremely poor prognosis. BAP1 is a tumor suppressor that has been associated with the outcome of melanomas and other malignancies. In this study, we investigated the genetic alterations in BAP1 and the prognostic potential of BAP1 protein expression in oral mucosal melanoma. DNA sequence analysis of BAP1 from 12 OMM patient samples revealed missense mutations in the tissues from four patients. Based on immunohistochemical staining, loss of nuclear BAP1 expression was associated with poor overall survival (P < 0...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399342/uveal-melanoma-treatment-and-prognostication
#5
Mehmet Dogrusöz, Martine J Jager, Bertil Damato
Approximately 90% of uveal melanoma develop in the choroid, with the remainder arising in the ciliary body or the iris. The treatment of uveal melanoma is aimed at conserving the eye and useful vision, and, if possible, preventing metastatic disease. Enucleation is now reserved for tumors that are large and/or involve the optic disc, having largely been replaced by various forms of radiotherapy (plaque brachy-therapy, proton beam or stereotactic radiotherapy) and laser therapy. Whereas iridectomy and iridocyclectomy are widely performed, transscleral exoresection of choroidal tumors is performed only in a few centers because it requires special skills and hypotensive anesthesia...
March 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28391358/genetic-evolution-of-uveal-melanoma-guides-the-development-of-an-inflammatory-microenvironment
#6
Gülçin Gezgin, Mehmet Dogrusöz, T Huibertus van Essen, Wilhelmina G M Kroes, Gregorius P M Luyten, Pieter A van der Velden, Vonn Walter, Robert M Verdijk, Thorbald van Hall, Sjoerd H van der Burg, Martine J Jager
Uveal melanoma (UM) is characterized by a number of genetic aberrations that follow a certain chronology and are tightly linked to tumor recurrence and survival. Loss of chromosome 3, bi-allelic loss of BAP1 expression, and gain in chromosome 8q have been associated with metastasis formation and death, while loss of chromosome 3 has been associated with the influx of macrophages and T cells. We used a set of genetically-classified UM to study immune infiltration in the context of their genetic evolution. We show in two independent cohorts that lack of BAP1 expression is associated with an increased density of CD3(+) T cells and CD8(+) T cells...
April 8, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28389374/a-novel-brca1-associated-protein-1-isoform-affects-response-of-mesothelioma-cells-to-drugs-impairing-brca1-mediated-dna-repair
#7
Rossella Parrotta, Agata Okonska, Manuel Ronner, Walter Weder, Rolf Stahel, Lorenza Penengo, Emanuela Felley-Bosco
INTRODUCTION: BRCA1-associated protein-1, BAP1, is a tumor suppressor involved in multiple cellular processes such as transcriptional regulation, chromatin modification by deubiquitinating histone 2A and DNA repair. BAP1 mutations are frequent in malignant pleural mesothelioma (MPM). Our aim was to functionally characterize a newly identified isoform of BAP1 and investigate the effects of its expression on drug sensitivity in MPM. METHODS: Expression of BAP1 isoforms was detected by qPCR in MPM and normal mesothelium cell lines, tumor and non-tumor samples...
April 4, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28362705/loss-of-bap1-expression-occurs-rarely-to-never-in-colorectal-adenocarcinoma
#8
Jeanie Chui, Brandon Verdonk, Anthony J Gill
No abstract text is available yet for this article.
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28347665/discovery-of-small-molecule-inhibitors-for-the-snake-venom-metalloprotease-bap1-using-in-silico-and-in-vitro-tests
#9
Fabian Villalta-Romero, Luiz Borro, Boris Mandic, Teresa Escalante, Alexandra Rucavado, Jose María Gutiérrez, Goran Neshich, Ljubica Tasic
Snakebites represent an important public health problem, with a great number of victims with permanent sequelae or fatal outcomes, particularly in rural, agriculturally active areas. The snake venom metalloproteases (SVMPs) are the principal proteins responsible for some clinically-relevant effects, such as local and systemic hemorrhage, dermonecrosis, and myonecrosis. Because of the difficulties in neutralizing them rapidly and locally by antivenoms, the search and design of small molecules as inhibitors of SVMPs are proposed...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28342657/targeting-bap1-a-new-paradigm-for-mesothelioma
#10
EDITORIAL
L M Schunselaar, W Zwart, P Baas
New treatment strategies for malignant pleural mesothelioma (MPM) are important. BAP1 mutations are present in 47-67% of the MPM tumors, making this a good target for treatment. Multiple functions of BAP1 are investigated in the preclinical situation. Due to many functions of BAP1, the phenotypic effect of BAP1 is diverse. Preclinical data on inhibitors reversing these phenotypic effects are promising. However, the mechanism of BAP1 is not fully elucidated yet and further research about the mechanism and possible inhibitors is necessary...
March 18, 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28339037/the-long-non-coding-rna-lncfoxo1-suppresses-growth-of-human-breast-cancer-cells-through-association-with-bap1
#11
Jie Xi, Jing Feng, Qian Li, Xia Li, Saitian Zeng
Breast cancer, one of the common cancers of women, is the leading cause of death among women below the age of 50 years in western countries. Long non-coding RNAs (lncRNAs) have been shown to be involved in diverse biological processes, both physical and pathological. However, to date, only a few lncRNAs have been functionally identified in breast cancer, and the overall pathophysiological contributions of lncRNAs to breast cancer remain largely unknown. In the present study, we identified a novel lncRNA termed lncFOXO1 through microarray screening...
March 24, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338651/dichotomy-in-intrahepatic-cholangiocarcinomas-based-on-histologic-similarities-to-hilar-cholangiocarcinomas
#12
Masayuki Akita, Kohei Fujikura, Tetsuo Ajiki, Takumi Fukumoto, Kyoko Otani, Takeshi Azuma, Tomoo Itoh, Yonson Ku, Yoh Zen
Intrahepatic cholangiocarcinomas were classified into two types based on their microscopic appearance. Tumors with histologic similarities to hilar cholangiocarcinomas (predominantly ductal adenocarcinomas with minor tubular components, if present, restricted to the invasive front) were defined as the perihilar type, whereas the others were classified as peripheral cholangiocarcinomas. Among the 47 cases examined in the present study, 26 (55%) were classified as the perihilar type, whereas 21 (45%) were the peripheral type...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28327999/comprehensive-genomic-profiling-of-salivary-mucoepidermoid-carcinomas-reveals-frequent-bap1-pik3ca-and-other-actionable-genomic-alterations
#13
K Wang, J D McDermott, A B Schrock, J A Elvin, L Gay, S D Karam, D Raben, H Somerset, S M Ali, J S Ross, D W Bowles
Background: We sought to identify genomic alterations (GAs) in salivary mucoepidermoid carcinomas. Patients and methods: DNA was extracted from 48 mucoepidermoid carcinomas. Comprehensive genomic profiling (CGP) including the calculation to tumor mutational burden (TMB) was performed on hybridization-captured adaptor ligation-based libraries of 315 cancer-related genes plus introns from 28 genes frequently rearranged for cancer and evaluated for all classes of GAs...
April 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327121/bap1-and-pbrm1-in-metastatic-clear-cell-renal-cell-carcinoma-tumor-heterogeneity-and-concordance-with-paired-primary-tumor
#14
Jeanette E Eckel-Passow, Daniel J Serie, John C Cheville, Thai H Ho, Payal Kapur, James Brugarolas, R Houston Thompson, Bradley C Leibovich, Eugene D Kwon, Richard W Joseph, Alexander S Parker
BACKGROUND: BAP1 and PBRM1 are frequently mutated in primary clear cell renal cell carcinoma (ccRCC) tumors; however, the frequency and clinical relevance of these mutations in metastatic ccRCC tumors is unknown. Additionally, while intra-tumor heterogeneity has been shown to be common in primary ccRCC, little is known regarding heterogeneity in metastatic ccRCC tumors. MATERIALS AND METHODS: We analyzed BAP1 and PBRM1 loss of protein expression in patient-matched primary and metastatic tumors from 97 patients...
March 21, 2017: BMC Urology
https://www.readbyqxmd.com/read/28284891/loss-of-bap1-protein-expression-in-the-first-metastatic-site-predicts-prognosis-in-patients-with-clear-cell-renal-cell-carcinoma
#15
Yuji Miura, Naoko Inoshita, Masaomi Ikeda, Yu Miyama, Ryosuke Oki, Suguru Oka, Chihiro Kondoh, Yukinori Ozaki, Yuko Tanabe, Kazuhiro Kurosawa, Shinji Urakami, Tadasu Kohno, Toshikazu Okaneya, Toshimi Takano
OBJECTIVES: To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value. METHODS AND MATERIALS: We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins...
March 8, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28283772/identification-genetic-testing-and-management-of-hereditary-melanoma
#16
Sancy A Leachman, Olivia M Lucero, Jone E Sampson, Pamela Cassidy, William Bruno, Paola Queirolo, Paola Ghiorzo
Several distinct melanoma syndromes have been defined, and genetic tests are available for the associated causative genes. Guidelines for melanoma genetic testing have been published as an informal "rule of twos and threes," but these guidelines apply to CDKN2A testing and are not intended for the more recently described non-CDKN2A melanoma syndromes. In order to develop an approach for the full spectrum of hereditary melanoma patients, we have separated melanoma syndromes into two types: "melanoma dominant" and "melanoma subordinate...
March 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28275095/bap1-inhibits-the-er-stress-gene-regulatory-network-and-modulates-metabolic-stress-response
#17
Fangyan Dai, Hyemin Lee, Yilei Zhang, Li Zhuang, Hui Yao, Yuanxin Xi, Zhen-Dong Xiao, M James You, Wei Li, Xiaoping Su, Boyi Gan
The endoplasmic reticulum (ER) is classically linked to metabolic homeostasis via the activation of unfolded protein response (UPR), which is instructed by multiple transcriptional regulatory cascades. BRCA1 associated protein 1 (BAP1) is a tumor suppressor with de-ubiquitinating enzyme activity and has been implicated in chromatin regulation of gene expression. Here we show that BAP1 inhibits cell death induced by unresolved metabolic stress. This prosurvival role of BAP1 depends on its de-ubiquitinating activity and correlates with its ability to dampen the metabolic stress-induced UPR transcriptional network...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28256910/brca1-associated-protein-1-suppresses-osteosarcoma-cell-proliferation-and-migration-through-regulation-pi3k-akt-pathway
#18
Shuming Gao, Hongjiang Sun, Cai Cheng, Guangya Wang
BRCA1-associated protein-1 (BAP1) is an important nuclear-localized deubiquitinating enzyme. Dysregulation of BAP1 has been reported in many types of cancers. However, there are few articles on the role of BAP1 in osteosarcoma (OS) and the molecular mechanisms of BAP1 in OS remain largely unknown. In this study, we examined the expression of BAP1 in the tissue sample from OS patients and healthy control subjects, and then investigated the biological function and molecular mechanisms of BAP1 in OS. We found that BAP1 was significantly reduced in OS patients and OS cell lines...
March 3, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28240745/the-biological-and-prognostic-significance-of-angiotropism-in-uveal-melanoma
#19
Raymond L Barnhill, Mengliang Ye, Aude Batistella, Marc-Henri Stern, Sergio Roman-Roman, Rémi Dendale, Olivier Lantz, Sophie Piperno-Neumann, Laurence Desjardins, Nathalie Cassoux, Claire Lugassy
Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy...
February 27, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28229253/the-biology-of-uveal-melanoma
#20
Adriana Amaro, Rosaria Gangemi, Francesca Piaggio, Giovanna Angelini, Gaia Barisione, Silvano Ferrini, Ulrich Pfeffer
Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11...
March 2017: Cancer Metastasis Reviews
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