scholarly journals The Importance of Multidisciplinary Approach in Early Detection of BAP1 Tumor Predisposition Syndrome: Clinical Management and Risk Assessment

2014 ◽  
Vol 8 ◽  
pp. CMO.S15239 ◽  
Author(s):  
Angelo Battaglia
Keyword(s):  
Gene Expression ◽  
Multidisciplinary Approach ◽  
Cancer Susceptibility ◽  
Published Data ◽  
Cancer Syndrome ◽  
Functional Studies ◽  
Interaction Partners ◽  
Definition Of ◽  
Tumor Types

Germline BAP1 (BRCA1-associated protein-1) mutations are involved into a novel specific cancer syndrome and strictly associated with a high cancer susceptibility. Recent data suggest that BAP1 has activity toward target substrates explaining why loss of BAP1 causes a pro-tumorigenic deregulation of gene expression. The recently published data reviewed raise the hypothesis that BAP1 regulates a common subset of substrates, which in turn causes a pro-tumorigenic deregulation of gene expression, and alternatively suggest the role of BAP1 as tumorigenesis suppressor/promoter also by independent mechanisms. The clinical phenotype of BAP1 alterations includes MBAITs (melanocytic BAP1-mutated atypical intradermal tumors), uveal melanoma (UM), cutaneous melanoma (CM), renal cell carcinoma (RCC), mesothelioma (MM), and possibly several other tumors. In clinical practice, early diagnosis is crucial for curative resection of all these tumor types. The uniformed and unambiguous definition of MBAITs as clinical/pathological predictive markers could provide physicians means to identify patients who may carry germline BAP1 mutations and thus could be at high risk of developing CM, UM, MM, RCC, and possibly other tumors. As part of a novel multidisciplinary approach, physicians, pathologists, and clinicians involved into diagnostics should be aware of the histological features and the spectrum of tumors associated with BAP1 loss. Further clinical, epidemiological, and functional studies are required to fully explain the roles of BAP1 and its interaction partners in neoplasia, to define mechanisms behind shared and non-shared clinical and pathological criteria.

scholarly journals Germline variant in REXO2 is a novel candidate gene in familial pheochromocytoma

2020 ◽  
Vol 102 ◽  
Author(s):  
Yael Laitman ◽  
Shay Tzur ◽  
Ruben Attali ◽  
Amit Tirosh ◽  
Eitan Friedman
Keyword(s):  
Allelic Imbalance ◽  
Chromosomal Region ◽  
Cancer Susceptibility ◽  
Functional Studies ◽  
Cancer Susceptibility Genes ◽  
Whole Exome ◽  
Familial Pheochromocytoma ◽  
The Family ◽  
Recombination Processes

Abstract Pheochromocytoma (PCC) is a rare, mostly benign tumour of the adrenal medulla. Hereditary PCC accounts for ~35% of cases and has been associated with germline mutations in several cancer susceptibility genes (e.g., KIF1B, SDHB, VHL, SDHD, RET). We performed whole-exome sequencing in a family with four PCC-affected patients in two consecutive generations and identified a potential novel candidate pathogenic variant in the REXO2 gene that affects splicing (c.531-1G>T (NM 015523.3)), which co-segregated with the phenotype in the family. REXO2 encodes for RNA exonuclease 2 protein and localizes to 11q23, a chromosomal region displaying allelic imbalance in PCC. REXO2 protein has been associated with DNA repair, replication and recombination processes and thus its inactivation may contribute to tumorigenesis. While the study suggests that this novel REXO2 gene variant underlies PCC in this family, additional functional studies are required in order to establish the putative role of the REXO2 gene in PCC predisposition.

scholarly journals The Emerging Role of PIWI-Interacting RNAs (piRNAs) in Gastrointestinal Cancers: An Updated Perspective

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 202
Author(s):  
Ismael Riquelme ◽  
Pablo Pérez-Moreno ◽  
Pablo Letelier ◽  
Priscilla Brebi ◽  
Juan Carlos Roa
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Molecular Characteristics ◽  
Clinical Markers ◽  
Rna Transcripts ◽  
Gi Cancers ◽  
Tumor Types ◽  
Cumulative Evidence

Gastrointestinal (GI) cancers produce ~3.4 million related deaths worldwide, comprising 35% of all cancer-related deaths. The high mortality among GI cancers is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not adequately guide patient management, thereby new and more reliable biomarkers and therapeutic targets are still needed for these diseases. RNA-seq technology has allowed the discovery of new types of RNA transcripts including PIWI-interacting RNAs (piRNAs), which have particular characteristics that enable these molecules to act via diverse molecular mechanisms for regulating gene expression. Cumulative evidence has described the potential role of piRNAs in the development of several tumor types as a likely explanation for certain genomic abnormalities and signaling pathways’ deregulations observed in cancer. In addition, these piRNAs might be also proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in malignancies. This review describes important topics about piRNAs including their molecular characteristics, biosynthesis processes, gene expression silencing mechanisms, and the manner in which these transcripts have been studied in samples and cell lines of GI cancers to elucidate their implications in these diseases. Moreover, this article discusses the potential clinical usefulness of piRNAs as biomarkers and therapeutic targets in GI cancers.

Tetraspanins in infections by human cytomegalo- and papillomaviruses

2017 ◽  
Vol 45 (2) ◽  
pp. 489-497 ◽  
Author(s):  
Laura A. Fast ◽  
Diana Lieber ◽  
Thorsten Lang ◽  
Luise Florin
Keyword(s):  
Plasma Membrane ◽  
Infectious Diseases ◽  
Cellular Membrane ◽  
Human Papillomaviruses ◽  
Cell Entry ◽  
Published Data ◽  
Interaction Partners ◽  
Host Cell Entry ◽  
Tetraspanin Family

Members of the tetraspanin family have been identified as essential cellular membrane proteins in infectious diseases by nearly all types of pathogens. The present review highlights recently published data on the role of tetraspanin CD151, CD81, and CD63 and their interaction partners in host cell entry by human cytomegalo- and human papillomaviruses. Moreover, we discuss a model for tetraspanin assembly into trafficking platforms at the plasma membrane. These platforms might persist during intracellular viral trafficking.

scholarly journals Pituitary Homeobox 1 Activates the Rat FSHβ (rFSHβ) Gene through Both Direct and Indirect Interactions with the rFSHβ Gene Promoter

2002 ◽  
Vol 16 (8) ◽  
pp. 1840-1852 ◽  
Author(s):  
Marjorie M. Zakaria ◽  
Kyeong-Hoon Jeong ◽  
Charlemagne Lacza ◽  
Ursula B. Kaiser
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Hormonal Regulation ◽  
Molecular Mechanisms ◽  
Specific Binding ◽  
Gene Promoter ◽  
Functional Studies ◽  
Direct Binding ◽  
Residual Activation

Abstract Molecular mechanisms underlying gonadotrope-specific and hormonal regulation of FSHβ gene expression remain largely unknown. We have studied the role of pituitary homeobox 1 (Ptx1), a transcription factor important for regulation of many pituitary-specific genes, in the regulation of rat FSHβ (rFSHβ) gene transcription. We demonstrate that Ptx1 activates the rFSHβ gene promoter both basally and in synergy with GnRH. The effect of Ptx1 was localized to −140/−50, a region also important for basal activity of the promoter. Two putative Ptx1 binding sites (P1 and P2) homologous to consensus Ptx1 binding elements were identified in this region. We demonstrate specific binding of Ptx1 to the P2 but not to the P1 site. Furthermore, functional studies indicate that the P2 but not the P1 site mediates activation of the promoter by Ptx1. Residual activation of the promoter by Ptx1 was observed independent of the P2 site. However, no additional Ptx1 binding sites were identified in this region, indicating that the residual activation observed is likely independent of direct Ptx1 binding to the promoter. These results identify a functional Ptx1 binding site in the rFSHβ gene promoter and suggest the presence of an additional activating pathway that is independent of direct binding of Ptx1 to the promoter.

scholarly journals Hybrid Convergent Procedure for the Treatment of Persistent and Long-standing Persistent Atrial Fibrillation

2021 ◽  
Vol 10 (3) ◽  
pp. 198-204
Author(s):  
David B DeLurgio ◽  
Jaswinder S Gill ◽  
Syed Ahsan ◽  
Riyaz A Kaba ◽  
Kristen M Plasseraud ◽  
...  
Keyword(s):  
Multidisciplinary Approach ◽  
Pulmonary Veins ◽  
Persistent Atrial Fibrillation ◽  
Rhythm Control ◽  
Published Data ◽  
Future Directions ◽  
Ablation Therapy ◽  
Treatment Gaps ◽  
Made In

Recent advances have been made in AF treatment, including the role of early rhythm control and landmark clinical trials using ablation therapy. However, some treatment gaps remain, including the creation of durable lesions outside the pulmonary veins and effective treatment of longstanding persistent AF. A novel epicardial-endocardial ablation approach – the hybrid convergent procedure – was developed to combine surgical and catheter ablation techniques into a collaborative, multidisciplinary approach to managing AF. In this review, the authors discuss recently published data on hybrid convergent ablation, including results of the CONVERGE clinical trial, in the context of current challenges to treatment of persistent and long-standing persistent AF. The review also aims to provide perspective on outstanding questions and future directions in this area.

C-Abl Regulates Mcl-1 Gene Expression In Chronic Lymphocytic Leukaemia Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3579-3579
Author(s):  
John C Allen ◽  
Mirko Zuzel ◽  
Ke Lin ◽  
Joseph R Slupsky
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Conflicts Of Interest ◽  
Strong Relationship ◽  
Chemotherapeutic Agents ◽  
Disease Prognosis ◽  
Stat3 Phosphorylation ◽  
Definition Of

Abstract Abstract 3579 Chronic lymphocytic leukaemia (CLL) is a prevalent malignancy characterised by the clonal expansion of mature B cells that are resistant to apoptosis. This resistance to apoptosis will partly be due to Mcl-1 expression because high levels of this protein in CLL cells correlate with poor disease prognosis and resistance to chemotherapy. Thus, understanding the mechanism(s) regulating Mcl-1 expression in CLL cells may be useful in the development of new therapies for this incurable disease. In the present study we show a strong relationship between c-Abl and Mcl-1 expression in CLL cells. We show that treatment of CLL cells with Abl-specific siRNA or with imatinib, to inhibit c-Abl activity, results in the downregulation of Mcl-1 protein and mRNA. A major regulator of Mcl-1 gene expression is STAT3. Our data show that CLL cells expressing high levels of c-Abl also show elevated levels of phospho-STAT3, and that STAT3 phosphorylation in CLL cells is dependent on c-Abl activity. However, STAT3 phosphorylation by c-Abl is not direct, and requires activation of NFkB, secretion of autocrine IL6 and active PKC. Taken together, our results provide clearer definition of the pathobiological role of c-Abl in CLL cells. Given that high NFkB activation, plasma IL6 levels and Mcl-1 all correlate with poor disease prognosis in CLL, our work potentially connects several features of CLL cells that are important to their pathophysiology by suggesting a central role of c-Abl in their regulation. Since CLL cells expressing high levels of c-Abl and Mcl-1 belong to the unmutated, poor prognostic group of CLL, c-Abl inhibition may have therapeutic application in the treatment of this disease, especially for those patients who are resistant to conventional chemotherapeutic agents. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Role of Viral Ribonucleoproteins in Human Papillomavirus Type 16 Gene Expression

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1110 ◽  
Author(s):  
Naoko Kajitani ◽  
Stefan Schwartz
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Rna Splicing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Human Papillomaviruses ◽  
Protein Coding ◽  
Human Papillomavirus Type 16 ◽  
Definition Of

Human papillomaviruses (HPVs) depend on the cellular RNA-processing machineries including alternative RNA splicing and polyadenylation to coordinate HPV gene expression. HPV RNA processing is controlled by cis-regulatory RNA elements and trans-regulatory factors since the HPV splice sites are suboptimal. The definition of HPV exons and introns may differ between individual HPV mRNA species and is complicated by the fact that many HPV protein-coding sequences overlap. The formation of HPV ribonucleoproteins consisting of HPV pre-mRNAs and multiple cellular RNA-binding proteins may result in the different outcomes of HPV gene expression, which contributes to the HPV life cycle progression and HPV-associated cancer development. In this review, we summarize the regulation of HPV16 gene expression at the level of RNA processing with focus on the interactions between HPV16 pre-mRNAs and cellular RNA-binding factors.

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