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https://www.readbyqxmd.com/read/28925401/endogenous-androgen-receptor-proteomic-profiling-reveals-genomic-subcomplex-involved-in-prostate-tumorigenesis
#1
S Stelloo, E Nevedomskaya, Y Kim, L Hoekman, O B Bleijerveld, T Mirza, L F A Wessels, W M van Weerden, A F M Altelaar, A M Bergman, W Zwart
Androgen receptor (AR) is a key player in prostate cancer development and progression. Here we applied immunoprecipitation mass spectrometry of endogenous AR in LNCaP cells to identify components of the AR transcriptional complex. In total, 66 known and novel AR interactors were identified in the presence of synthetic androgen, most of which were critical for AR-driven prostate cancer cell proliferation. A subset of AR interactors required for LNCaP proliferation were profiled using chromatin immunoprecipitation assays followed by sequencing, identifying distinct genomic subcomplexes of AR interaction partners...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28808656/hoxb9-expression-correlates-with-histological-grade-and-prognosis-in-lscc
#2
Chuanhui Sun, Changsong Han, Peng Wang, Yinji Jin, Yanan Sun, Lingmei Qu
The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28798948/hoxb13-mutations-and-binding-partners-in-prostate-development-and-cancer-function-clinical-significance-and-future-directions
#3
Hannah Brechka, Raj R Bhanvadia, Calvin VanOpstall, Donald J Vander Griend
The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research. An enhanced understanding of HOX signaling, and the co-factors regulating HOX protein specificity and transcriptional regulation, has the high potential to elucidate novel approaches to prevent, diagnose, stage, and treat prostate cancer. Toward our understanding of HOX biology in prostate development and prostate cancer, basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology...
June 2017: Genes & Diseases
https://www.readbyqxmd.com/read/28790484/inherited-predisposition-to-prostate-cancer-from-gene-discovery-to-clinical-impact
#4
Kathleen A Cooney
Family history of prostate cancer is one of the three most important risk factors for the disease in addition to age and race. Yet despite the recognition of this significant heritable component, it has been challenging to identify the genes associated with prostate cancer predisposition. Initial approaches focused on the collection of multiplex prostate cancer families. However, despite more than 20 years of linkage studies, few genes have been identified that account for a significant number of hereditary prostate cancer families...
2017: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/28783165/tmprss2-erg-fusion-co-opts-master-transcription-factors-and-activates-notch-signaling-in-primary-prostate-cancer
#5
Ken J Kron, Alexander Murison, Stanley Zhou, Vincent Huang, Takafumi N Yamaguchi, Yu-Jia Shiah, Michael Fraser, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow, Mathieu Lupien
TMPRSS2-ERG (T2E) structural rearrangements typify ∼50% of prostate tumors and result in overexpression of the ERG transcription factor. Using chromatin, genomic and expression data, we show distinct cis-regulatory landscapes between T2E-positive and non-T2E primary prostate tumors, which include clusters of regulatory elements (COREs). This difference is mediated by ERG co-option of HOXB13 and FOXA1, implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression...
September 2017: Nature Genetics
https://www.readbyqxmd.com/read/28657667/germline-genetic-variants-in-men-with-prostate-cancer-and-one-or-more-additional-cancers
#6
Patrick G Pilié, Anna M Johnson, Kristen L Hanson, Megan E Dayno, Ashley L Kapron, Elena M Stoffel, Kathleen A Cooney
BACKGROUND: Prostate cancer has a significant heritable component, and rare deleterious germline variants in certain genes can increase the risk of the disease. The aim of the current study was to describe the prevalence of pathogenic germline variants in cancer-predisposing genes in men with prostate cancer and at least 1 additional primary cancer. METHODS: Using a multigene panel, the authors sequenced germline DNA from 102 men with prostate cancer and at least 1 additional primary cancer who also met ≥1 of the following criteria: 1) age ≤55 years at the time of diagnosis of the first malignancy; 2) rare tumor type or atypical presentation of a common tumor; and/or 3) ≥3 primary malignancies...
June 28, 2017: Cancer
https://www.readbyqxmd.com/read/28555048/sensitivity-of-hoxb13-as-a-diagnostic-immunohistochemical-marker-of-prostatic-origin-in-prostate-cancer-metastases-comparison-to-psa-prostein-androgen-receptor-erg-nkx3-1-psap-and-psma
#7
Ilka Kristiansen, Carsten Stephan, Klaus Jung, Manfred Dietel, Anja Rieger, Yuri Tolkach, Glen Kristiansen
AIMS: Determining the origin of metastases is an important task of pathologists to allow for the initiation of a tumor-specific therapy. Recently, homeobox protein Hox-B13 (HOXB13) has been suggested as a new marker for the detection of prostatic origin. The aim of this study was to evaluate the diagnostic sensitivity of HOXB13 in comparison to commonly used immunohistochemical markers for prostate cancer. MATERIALS AND METHODS: Histologically confirmed prostate cancer lymph node metastases from 64 cases were used to test the diagnostic value of immunohistochemical markers: prostate specific antigen (PSA), Prostatic acid phosphatase (PSAP), prostate specific membrane antigen (PSMA), homeobox gene NKX3...
May 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28484843/hoxb13-a-useful-marker-in-pleomorphic-giant-cell-adenocarcinoma-of-the-prostate-a-case-report-and-review-of-the-literature
#8
REVIEW
Laura Larnaudie, Eva Compérat, Pierre Conort, Justine Varinot
We report the case of an 81-year-old patient with a pleomorphic giant cell adenocarcinoma of the prostate. After diagnosis, he rapidly developed bone metastasis and died within 1 year. This variant of acinar adenocarcinoma is extremely rare and prognosis is poor. This entity has been included into the 2016 WHO classification. The principal differential diagnosis is urothelial carcinoma. To assess the prostatic origin, routine immunohistochemistry can be problematic. Loss of epitopes in this poorly differentiated entity can occur, such as loss of expression of PSA and p504s...
July 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28442163/the-search-for-the-missing-heritability-of-prostate-cancer
#9
EDITORIAL
Patrick C Walsh
Scientists and clinicians at Johns Hopkins have been working since 1987 to uncover the genetic pathogenesis of prostate cancer. A patient query about the hereditary nature of the disease led to data collection on family history, followed by segregation and linkage analyses. Collaborative investigations using next-generation sequencing to identify genetic variants associated with prostate cancer risk have revealed the significance of HOXB13, BRCA 1/2, and DNA repair mutations.
April 22, 2017: European Urology
https://www.readbyqxmd.com/read/28402266/expression-signatures-of-hox-cluster-genes-in-cervical-cancer-pathogenesis-impact-of-human-papillomavirus-type-16-oncoprotein-e7
#10
Sweta Sharma Saha, Rahul Roy Chowdhury, Nidhu Ranjan Mondal, Sudipta Roy, Sharmila Sengupta
The Homeobox (HOX) genes encode important transcription factors showing deregulated expression in several cancers. However, their role in cervical cancer pathogenesis, remains largely unexplored. Herein, we studied their association with Human Papillomavirus type 16 (HPV16) mediated cervical cancers. Our previously published gene expression microarray data revealed a significant alteration of 12 out of 39 HOX cluster members among cervical cancer cases, in comparison to the histopathologically normal controls...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28272408/computational-modeling-of-complete-hoxb13-protein-for-predicting-the-functional-effect-of-snps-and-the-associated-role-in-hereditary-prostate-cancer
#11
Gopalakrishnan Chandrasekaran, Eu Chang Hwang, Taek Won Kang, Dong Deuk Kwon, Kwangsung Park, Je-Jung Lee, Vinoth-Kumar Lakshmanan
The human HOXB13 gene encodes a 284 amino acid transcription factor belonging to the homeobox gene family containing a homeobox and a HoxA13 N-terminal domain. It is highly linked to hereditary prostate cancer, the majority of which is manifested as a result of a Single Nucleotide Polymorphism (SNP). In silico analysis of 95 missense SNP's corresponding to the non-homeobox region of HOXB13 predicted 21 nsSNP's to be potentially deleterious. Among 123 UTR SNPs analysed by UTRScan, rs543028086, rs550968159, rs563065128 were found to affect the UNR_BS, GY-BOX and MBE UTR signals, respectively...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28186998/somatic-molecular-subtyping-of-prostate-tumors-from-hoxb13-g84e-carriers
#12
Tamara L Lotan, Alba Torres, Miao Zhang, Jeffrey J Tosoian, Liana B Guedes, Helen Fedor, Jessica Hicks, Charles M Ewing, Sarah D Isaacs, Dorhyun Johng, Angelo M De Marzo, William B Isaacs
A recurrent germline mutation (G84E) in the HOXB13 gene is associated with early onset and family history-positive prostate cancer in patients of European descent, occurring in up to 5% of prostate cancer families. To date, the molecular features of prostate tumors occurring in HOXB13 G84E carriers have not been studied in a large cohort of patients. We identified 101 heterozygous carriers of G84E who underwent radical prostatectomy for prostate cancer between 1985 and 2011 and matched these men by race, age and tumor grade to 99 HOXB13 wild-type controls...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28072499/in-silico-analysis-of-the-deleterious-nssnps-missense-in-the-homeobox-domain-of-human-hoxb13-gene-responsible-for-hereditary-prostate-cancer
#13
Gopalakrishnan Chandrasekaran, Eu Chang Hwang, Taek Won Kang, Dong Deuk Kwon, Kwangsung Park, Je-Jung Lee, Vinoth-Kumar Lakshmanan
The human HOXB13 gene encodes a transcription factor containing a DNA-binding homeobox domain and a HoxA13 N-terminal domain. SNP is considered to be the primary genetic cause for hereditary prostate cancer (PCa). The study of functional nsSNPs would give an insight into the exact cause underlying the onset of hereditary PCa and possible methodologies for the cure or early management of the disease. Several in silico tools were used to screen and map the deleterious nsSNPs to the protein structure for predicting the structure-function effects...
August 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27956498/h3k27-acetylation-activated-long-non-coding-rna-ccat1-affects-cell-proliferation-and-migration-by-regulating-spry4-and-hoxb13-expression-in-esophageal-squamous-cell-carcinoma
#14
Erbao Zhang, Liang Han, Dandan Yin, Xuezhi He, Linzhi Hong, Xinxin Si, Mantang Qiu, Tongpeng Xu, Wei De, Lin Xu, Yongqian Shu, Jinfei Chen
Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. In our study, we found that lncRNA CCAT1, whose expression is significantly increased and is correlated with outcomes in Esophageal Squamous Cell Carcinoma (ESCC). Consecutive experiments confirmed that H3K27-acetylation could activate expression of colon cancer associated transcript-1 (CCAT1). Further experiments revealed that CCAT1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27902461/whole-exome-sequencing-in-75-high-risk-families-with-validation-and-replication-in-independent-case-control-studies-identifies-tango2-or5h14-and-chad-as-new-prostate-cancer-susceptibility-genes
#15
Danielle M Karyadi, Milan S Geybels, Eric Karlins, Brennan Decker, Laura McIntosh, Amy Hutchinson, Suzanne Kolb, Shannon K McDonnell, Belynda Hicks, Sumit Middha, Liesel M FitzGerald, Melissa S DeRycke, Meredith Yeager, Daniel J Schaid, Stephen J Chanock, Stephen N Thibodeau, Sonja I Berndt, Janet L Stanford, Elaine A Ostrander
Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families. Analysis of 341 candidate risk variants identified nine variants significantly associated with increased PCa risk in a population-based, case-control study of 2,495 men...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27899188/familial-prostate-cancer
#16
Veda N Giri, Jennifer L Beebe-Dimmer
Prostate cancer is the most commonly diagnosed cancer among men in the United States as well as most Western countries. A significant proportion of men report having a positive family history of prostate cancer in a first-degree relative (father, brother, son), which is important in that family history is one of the only established risk factors for the disease and plays a role in decision-making for prostate cancer screening. Familial aggregation of prostate cancer is considered a surrogate marker of genetic susceptibility to developing the disease, but shared environment cannot be excluded as an explanation for clustering of cases among family members...
October 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27819754/urological-cancer-related-to-familial-syndromes
#17
REVIEW
Walter Henriques da Costa, George Jabboure, Isabela Werneck da Cunha
Cancer related to hereditary syndromes corresponds to approximately 5-10% of all tumors. Among those from the genitourinary system, many tumors had been identified to be related to genetic syndromes in the last years with the advent of new molecular genetic tests. New entities were described or better characterized, especially in kidney cancer such as hereditary leiomyomatosis renal cell carcinoma (HLRCC), succinate dehydrogenase kidney cancer (SDH-RCC), and more recently BAP1 germline mutation related RCC...
March 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/27749322/clinical-validity-of-detecting-circulating-tumor-cells-by-adnatest-assay-compared-with-direct-detection-of-tumor-mrna-in-stabilized-whole-blood-as-a-biomarker-predicting-overall-survival-for-metastatic-castration-resistant-prostate-cancer-patients
#18
COMPARATIVE STUDY
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
https://www.readbyqxmd.com/read/27701467/germline-variants-of-prostate-cancer-in-japanese-families
#19
Takahide Hayano, Hiroshi Matsui, Hirofumi Nakaoka, Nobuaki Ohtake, Kazuyoshi Hosomichi, Kazuhiro Suzuki, Ituro Inoue
Prostate cancer (PC) is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family)...
2016: PloS One
https://www.readbyqxmd.com/read/27626483/association-between-germline-homeobox-b13-hoxb13-g84e-allele-and-prostate-cancer-susceptibility-a-meta-analysis-and-trial-sequential-analysis
#20
Jianzhong Zhang, Li Xiao, Zhiqiang Qin, Aiming Xu, Kai Zhao, Chao Liang, Chenkui Miao, Jundong Zhu, Wei Chen, Yibo Hua, Yiyang Liu, Chao Zhang, Yajie Yu, Shifeng Su, Zengjun Wang
Germline HOXB13 G84E mutation (rs138213197) has been described associated with prostate cancer (PCa) susceptibility but results of different studies are inconsistent. We conducted this meta-analysis to evaluate the specific role of this mutation. Relevant available studies were identified by searching the databases Pubmed, Embase and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. Subgroup analysis were performed to evaluate the specific role of rs138213197 in disease aggressiveness, diagnostic age and family history...
October 11, 2016: Oncotarget
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