scholarly journals Recent Advances in the Genetic of MALT Lymphomas

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 176
Author(s):  
Juan José Rodríguez-Sevilla ◽  
Antonio Salar
Keyword(s):  
Malt Lymphoma ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Chromosomal Translocations ◽  
Immunoglobulin Gene ◽  
Gene Usage ◽  
Frequent Mutations ◽  
Push Forward ◽  
Anatomic Locations

Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.

scholarly journals Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors

2009 ◽  
Vol 16 (1) ◽  
pp. 301-310 ◽  
Author(s):  
Yong Lin ◽  
Xiaofei Jiang ◽  
Ye Shen ◽  
Min Li ◽  
Huili Ma ◽  
...  
Keyword(s):  
Pituitary Tumors ◽  
Disease Recurrence ◽  
Genetic Alterations ◽  
Protein Overexpression ◽  
Akt Signaling Pathway ◽  
Real Time Quantitative Pcr ◽  
Frequent Mutations ◽  
Phosphoinositide 3 Kinase ◽  
First Time

Genetic alterations in the PIK3CA gene of the phosphoinositide 3-kinase (PI3K)/AKT pathway have been found in many human tumors, but they have not been explored in pituitary tumors. We undertook the present study to explore mutations and amplifications of the PIK3CA gene in pituitary tumors. DNA sequencing and real-time quantitative PCR were used to examine mutations and amplifications respectively, on genomic DNA samples isolated from 353 cases of pituitary tumors, and immunohistostaining was used to assess PIK3CA expression. About 8 out of 91 (9%) invasive pituitary tumors versus 0 out of 262 (0%) noninvasive tumors were found to harbor somatic mutations in exons 9 and 20 of the PIK3CA gene (P<0.001), and the mutation was associated with increased disease recurrence. Genomic PIK3CA amplifications (defined as ≥4 copies) were observed in both invasive and noninvasive tumors, with a prevalence of around 20–40% in various types of pituitary tumors. PIK3CA protein overexpression was observed in cases with high PIK3CA copy number. RAS mutations were also examined and found in 6 out of the 91 (7%) invasive tumors. PIK3CA amplifications were mutually exclusive with PIK3CA or RAS mutations (P<0.001). This study demonstrated for the first time relatively common PIK3CA mutations and amplifications as well as RAS mutations and their tendency of mutual exclusivity in pituitary tumors. The data provide strong genetic evidence supporting a role of the PI3K/AKT signaling pathway in the tumorigenesis of pituitary tumors, particularly the invasive types.

THE ROLE OF PHOSPHATIDYLINOSITOL-3-KINASE IN CARCINOGENESIS

2017 ◽  
Vol 63 (4) ◽  
pp. 545-556
Author(s):  
Natalya Oskina ◽  
Aleksandr Shcherbakov ◽  
Maksim Filipenko ◽  
Nikolay Kushlinskiy ◽  
L. Ovchinnikova
Keyword(s):  
Genetic Disease ◽  
Intracellular Signaling ◽  
Somatic Mutations ◽  
Pi3k Pathway ◽  
Genetic Alterations ◽  
Phosphatidylinositol 3 Kinase ◽  
Intracellular Signaling Pathway ◽  
Metabolic Activities ◽  
Carcinogenic Process

Currently it is established that cancer is a genetic disease and that somatic mutations are the initiators of the carcinogenic process. The PI3K/AKT/mTOR pathway is an important intracellular signaling pathway regulating the cell growth and metabolic activities. Aberrant activation of the PI3K pathway is commonly observed in many different cancers. In this review we analyze the genetic alterations of PI3K pathway in a variety of human malignancies and discuss their possible implications for diagnosis and therapy.

scholarly journals Mutated p53 in HGSC—From a Common Mutation to a Target for Therapy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3465
Author(s):  
Aya Saleh ◽  
Ruth Perets
Keyword(s):  
Cancer Progression ◽  
Target Genes ◽  
P53 Protein ◽  
Genetic Alterations ◽  
Common Mutation ◽  
Missense Mutations ◽  
P53 Expression ◽  
Histologic Subtype ◽  
Tp53 Mutations

Mutations in tumor suppressor gene TP53, encoding for the p53 protein, are the most ubiquitous genetic variation in human ovarian HGSC, the most prevalent and lethal histologic subtype of epithelial ovarian cancer (EOC). The majority of TP53 mutations are missense mutations, leading to loss of tumor suppressive function of p53 and gain of new oncogenic functions. This review presents the clinical relevance of TP53 mutations in HGSC, elaborating on several recently identified upstream regulators of mutant p53 that control its expression and downstream target genes that mediate its roles in the disease. TP53 mutations are the earliest genetic alterations during HGSC pathogenesis, and we summarize current information related to p53 function in the pathogenesis of HGSC. The role of p53 is cell autonomous, and in the interaction between cancer cells and its microenvironment. We discuss the reduction in p53 expression levels in tumor associated fibroblasts that promotes cancer progression, and the role of mutated p53 in the interaction between the tumor and its microenvironment. Lastly, we discuss the potential of TP53 mutations to serve as diagnostic biomarkers and detail some more advanced efforts to use mutated p53 as a therapeutic target in HGSC.

scholarly journals LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Feifei Zhang ◽  
Hui Wang ◽  
Jiang Yu ◽  
Xueqing Yao ◽  
Shibin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Alternative Splicing ◽  
Noncoding Rna ◽  
De Novo ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Clinical Samples ◽  
Autophagy Flux ◽  
Resistance To Chemotherapy

AbstractDe novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.

scholarly journals Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3395
Author(s):  
Maria Radanova ◽  
Galya Mihaylova ◽  
Neshe Nazifova-Tasinova ◽  
Mariya Levkova ◽  
Oskan Tasinov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Targets ◽  
Clinicopathological Characteristics ◽  
Circular Rnas ◽  
Diagnostic Biomarkers ◽  
The Third ◽  
Current Review ◽  
Important Challenge ◽  
Prediction Of Metastasis

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.

scholarly journals Insights into the role of genetic alterations in adrenocortical tumorigenesis

2009 ◽  
Vol 300 (1-2) ◽  
pp. 169-174 ◽  
Author(s):  
M. Herbet ◽  
J.J. Feige ◽  
M. Thomas
Keyword(s):  
Genetic Alterations

scholarly journals V(D)J recombination: signal and coding joint resolution are uncoupled and depend on parallel synapsis of the sites.

1993 ◽  
Vol 13 (3) ◽  
pp. 1363-1370 ◽  
Author(s):  
K M Sheehan ◽  
M R Lieber
Keyword(s):  
Genome Stability ◽  
Lymphoid Cells ◽  
Chromosomal Translocations ◽  
Synaptic Inhibition ◽  
Site Specific ◽  
Coding Sequences ◽  
Specific Process ◽  
A Site ◽  
Joint Resolution

V(D)J recombination in lymphoid cells is a site-specific process in which the activity of the recombinase enzyme is targeted to signal sequences flanking the coding elements of antigen receptor genes. The order of the steps in this reaction and their mechanistic interdependence are important to the understanding of how the reaction fails and thereby contributes to genomic instability in lymphoid cells. The products of the normal reaction are recombinant joints linking the coding sequences of the receptor genes and, reciprocally, the signal ends. Extrachromosomal substrate molecules were modified to inhibit the physical synapsis of the recombination signals. In this way, it has been possible to assess how inhibiting the formation of one joint affects the resolution efficiency of the other. Our results indicate that signal joint and coding joint formation are resolved independently in that they can be uncoupled from each other. We also find that signal synapsis is critical for the generation of recombinant products, which greatly restricts the degree of potential single-site cutting that might otherwise occur in the genome. Finally, inversion substrates manifest synaptic inhibition at much longer distances than do deletion substrates, suggesting that a parallel rather than an antiparallel alignment of the signals is required during synapsis. These observations are important for understanding the interaction of V(D)J signals with the recombinase. Moreover, the role of signal synapsis in regulating recombinase activity has significant implications for genome stability regarding the frequency of recombinase-mediated chromosomal translocations.

scholarly journals The features of host immune response with respect to microsatellite status of colorectal cancer

2007 ◽  
Vol 15 (1-2) ◽  
pp. 5-9
Author(s):  
Attila Fenyvesi
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Immune Responses ◽  
Continuous Production ◽  
Tumor Infiltrating Lymphocytes ◽  
Host Immune Response ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Melting Point Analysis ◽  
Peritumoral Stroma

Background: The genetic alterations in colorectal cancer (CRC) progression are determined by two separate pathways, chromosomal and microsatellite instability (MSI). The CRCs with MSI have distinct clinicopathological characteristics with pronounced tumor-associated immune responses. The aim of our study was to investigate the intensity of host immune response in CRC tissue by comparing microsatellite stable (MSS) and instable tumors. Methods: The study was performed on CRC specimens from 28 patients with MSI and compared with 30 MSS tumors. The microsatellite status was evaluated with two markers by PCR and melting point analysis. The immunostaining with anti-CD3 pan-T cell antibody was used to quantify the number of tumor infiltrating lymphocytes. The lymphocytes in peritumoral stromal and the Crohn?s-like peritumoral reaction were counted on H&E slides. Results: No significant differences were found in the average number of lymphocytes in peritumoral stroma and in clinicopathological characteristics of CRCs. The conspicuous Crohn?s-like lymphoid reactions were present in 67.86% of CRCs with MSI versus 26.66% of MSS cases. The CRCs with MSI cases carried significantly higher numbers of tumor infiltrating T-lymphocytes (13.21 versus 7.47) (p<0.0001). Conclusion: The presences of peritumoral Crohn?s-like lymphoid and intraepithelial lymphocytic reaction were intensive markers for MSI in colorectal carcinomas in our study. The peculiar genetic instability in MSI tumors may lead to a continuous production of abnormal peptides, which act as neoantigens. They could induce specific antitumor immune responses effective in limiting tumor growth and spread. Abnormal peptides are potentially promising in immunotherapy advancing and in the design of a vaccine against colorectal tumors with MSI.

scholarly journals INFECTIOUS AETIOLOGY OF MARGINAL ZONE LYMPHOMA AND ROLE OF ANTI-INFECTIVE THERAPY

2016 ◽  
Vol 8 ◽  
pp. 2016006 ◽  
Author(s):  
Salvatore Perrone ◽  
Gianna Maria D'Elia ◽  
Alessandro Pulsoni
Keyword(s):  
Malt Lymphoma ◽  
Marginal Zone ◽  
Case Reports ◽  
Lymphocyte Activation ◽  
Chlamydia Psittaci ◽  
Gastric Malt Lymphoma ◽  
First Line Therapy ◽  
Causative Relationship ◽  
Chronic Hcv

Marginal zone lymphomas have been associated with several infectious agents covering both viral and bacterial pathogens and in some cases a clear aetiological role has been established. Pathogenetic mechanisms are currently not completely understood, however the role of chronic stimulation of the host immune response with persistent lymphocyte activation represents the most convincing explanation for lymphoproliferation. Gastric MALT lymphoma is strictly associated with Helicobacter pylori infection and various eradicating protocols, developed due to increasing antibiotic resistance, represent the first line therapy. The response rate to eradication is good with 80% of response at 1 year; this finding is also noteworthy because recapitulates a cancer cured only by antibacterial approach and it satisfies the Koch postulates of causation, establishing a causative relationship between Hp and gastric MALT lymphoma. Patients with chronic HCV infection have 5 times higher risk to develop MZL, in particular an association with splenic and nodal MZL has been shown in several studies. Moreover, there is evidence of lymphoma regression after antiviral therapy with interferon+ribavirin, thus rising hope that new available drugs, extremely effective against HCV replication, could improve outcome also in HCV-driven lymphomas. The rare cases of MZL localized to orbital fat and eye conjunctivas have been associated with Chlamydia psittaci infection carried by birds. Efficacy of antibacterial therapy against C. psittaci are conflicting and generally poorer thain gastric MALT. Finally some case-reports will cover the relationship between primary cutaneous B-cell Lymphomas and Borrelia Burgdorferi.

The role of molecular genetic alterations in genes involved in folate and homocysteine metabolism in multifactorial diseases pathogenesis

2017 ◽  
Vol 53 (5) ◽  
pp. 528-541
Author(s):  
A. M. Burdennyy ◽  
V. I. Loginov ◽  
T. M. Zavarykina ◽  
E. A. Braga ◽  
A. A. Kubatiev
Keyword(s):  
Molecular Genetic ◽  
Genetic Alterations ◽  
Multifactorial Diseases
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