scholarly journals The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1169 ◽  
Author(s):  
Sioletic Stefano ◽  
Scambia Giovanni
Keyword(s):  
Soft Tissue ◽  
Tumor Suppressor ◽  
Soft Tissue Sarcoma ◽  
Biological Significance ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Suppressor Gene ◽  
Oncogenic Signaling ◽  
Tensin Homolog ◽  
Pathologic Features

Soft tissue sarcoma (STS) is a rare malignancy of mesenchymal origin classified into more than 50 different subtypes with distinct clinical and pathologic features. Despite the poor prognosis in the majority of patients, only modest improvements in treatment strategies have been achieved, largely due to the rarity and heterogeneity of these tumors. Therefore, the discovery of new prognostic and predictive biomarkers, together with new therapeutic targets, is of enormous interest. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor that commonly loses its function via mutation, deletion, transcriptional silencing, or protein instability, and is frequently downregulated in distinct sarcoma subtypes. The loss of PTEN function has consequent alterations in important pathways implicated in cell proliferation, survival, migration, and genomic stability. PTEN can also interact with other tumor suppressors and oncogenic signaling pathways that have important implications for the pathogenesis in certain STSs. The aim of the present review is to summarize the biological significance of PTEN in STS and its potential role in the development of new therapeutic strategies.

scholarly journals Genomic loss of the putative tumor suppressor gene E2A in human lymphoma

2011 ◽  
Vol 208 (8) ◽  
pp. 1585-1593 ◽  
Author(s):  
Anne Steininger ◽  
Markus Möbs ◽  
Reinhard Ullmann ◽  
Karl Köchert ◽  
Stephan Kreher ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Progression ◽  
Treatment Strategies ◽  
Suppressor Gene ◽  
Lymphoid Cells ◽  
Oncogenic Signaling ◽  
Putative Tumor Suppressor Gene ◽  
Ras Pathway ◽  
New Treatment

The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.

Soft Tissue Sarcoma – a Current Review of the Diagnostic and Treatment Strategies

2019 ◽  
Vol 157 (06) ◽  
pp. 644-653 ◽  
Author(s):  
Sebastian Scheidt ◽  
Cornelius Jacobs ◽  
Sebastian Koob ◽  
Kristian Welle ◽  
Sebastian Walter ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Treatment Algorithm ◽  
Treatment Strategies ◽  
Soft Tissue Sarcomas ◽  
Current Evidence ◽  
Delayed Treatment ◽  
Current Review ◽  
Soft Tissue Swelling ◽  
A Current

AbstractSoft tissue sarcomas are a heterogeneous group of neoplasias that due to their often clinically silent appearance often remain undetected or experience delayed treatment. Especially soft tissue swelling is often misinterpreted by patients and doctors and trivialized or verified with an incorrect biopsy technique. The hereby evoked complications for the patients are serious and may be reduced by simply following the available guidelines. The treatment of soft tissue sarcomas requires a close interdisciplinary coordination between specialists in tumor orthopedics, oncology, radiology, pathology and radiotherapy. On the basis of a selective literature review, the following article points out the current evidence on the treatment and illustrates a treatment algorithm.

Translational significance of a newly identified hepatocellular carcinoma tumor suppressor gene on chromosome 8p.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15097-e15097
Author(s):  
Han Chong Toh ◽  
Francis Enane ◽  
Marissa Teo ◽  
Hideki Makishima ◽  
JoAnna Ng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Biological Significance ◽  
Suppressor Gene ◽  
Cell Cycle Exit ◽  
Malignant Liver

e15097 Background: After deletion of 17p that removes the tumor suppressor gene (TSG) TP53, deletion of 8p is the next most common chromosome abnormality in hepatocellular carcinoma (HCC). However, 8p TSG are insufficiently defined. Methods: Integrated genomic analysis of HCC and non-malignant liver obtained at therapeutic segmentectomy from the same patients. Results: A minimally deleted region on 8p was identified by SNP array. This incorporated GATA4. Therefore, GATA4 was Sanger sequenced in paired HCC/non-malignant liver: recurrent somatic non-synonymous missense mutations were identified in exon 4 (V267M n=5) or exon 6 (S357T n=6, R362N n=2, T366R n=2). Biallelic abnormalities were deletion and mutation (n=6) or mutation and uniparental disomy (n=4), with mutation or deletion of at least one GATA4 allele in 29/47 (62%) of HCC cases. The other GATA4 exons were mutation free. Although missense mutation is not intrinsically expected to decrease GATA4 expression, GATA4 mRNA was significantly decreased in cases with mutation as well as deletion (p<0.01) compared to non-malignant liver or wild-type GATA4 HCC. GATA4 drives liver differentiation, and the biological significance of GATA4 deficiency was demonstrated by significant enrichment (49%) for liver differentiation genes (p<1.2exp-124, Benjamini corrected) amongst genes with decreased expression in HCC compared to non-malignant liver. From an oncogenesis perspective, the most important of these hepatocyte genes (e.g., HNF4A, CEBPD) antagonize MYC to terminate proliferation: GATA4 introduction (expression vector) into HCC cells containing mutated or deleted GATA4 (HepG2 and PLC respectively) restored HNF4A and CEBPD expression, suppressed MYC protein, upregulated p27/CDKN1B that mediates cell cycle exit by maturation and significantly decreased HCC proliferation without apoptosis. In objectively quantified immunohistochemical analyses (ImageIQ), HCC cases with GATA4 mutation/deletion had significantly increased MYC protein (p<0.05). Conclusions: 8p deletion/GATA4 mutation in HCC suppresses cell cycle exit by maturation, thus complementing 17p deletion that suppresses cell cycle exit by apoptosis.

Predictive biomarkers of trabectedin (TR) and olaparib (OL) synergism in preclinical models of bone and soft tissue sarcoma (BSTS).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 10569-10569
Author(s):  
Ymera Pignochino ◽  
Federica Capozzi ◽  
Carmine Dell' Aglio ◽  
Marco Basiricò ◽  
Annalisa Lorenzato ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Predictive Biomarkers ◽  
Preclinical Models

Novel treatment strategies for soft tissue sarcoma

2007 ◽  
Vol 62 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Bernd Kasper ◽  
Thierry Gil ◽  
Veronique D’Hondt ◽  
Michael Gebhart ◽  
Ahmad Awada
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Treatment Strategies ◽  
Novel Treatment ◽  
Novel Treatment Strategies

scholarly journals Precision Medicine in Soft Tissue Sarcoma Treatment

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 221 ◽  
Author(s):  
Kenji Nakano ◽  
Shunji Takahashi
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Targeted Therapies ◽  
Antitumor Agents ◽  
Treatment Strategies ◽  
Genetic Mutation ◽  
Histological Subtypes ◽  
Genome Profiling ◽  
Number Of Patients ◽  
Precision Therapy

Soft tissue sarcoma (STS) is a rare component of malignant diseases. STS includes various histological subtypes, and there are some important differences among the different histological subtypes regarding the mutation profile and sensitivity to antitumor agents. Many clinical trials of STS incorporating many different histological subtypes in various populations have been conducted; it is difficult to compare the findings and make conclusions about clinical efficacy. Targeted therapies focusing on specific histological subtypes and precision therapy focusing on the specific genetic mutation(s) of each STS patient are being investigated. Since STS patients are a small population, new clinical trial designs are required to evaluate and establish new targeted therapies for each histological subtype that has a limited number of patients, and preclinical investigations are needed to detect targetable mutations. Now that cancer genome profiling is used in clinical practice, it is urgently necessary to connect the genome profiling data obtained in clinical settings to the optimal clinical treatment strategies. Herein we review the development and challenges of precision therapy in the management of STS patients.

scholarly journals Preoperative Factors Associated with Infiltrative Histologic Growth Patterns in Extremity Soft Tissue Sarcoma

Sarcoma ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jong Woong Park ◽  
Han-Soo Kim ◽  
Cheol Lee ◽  
Hye Jin Yoo ◽  
Ji Yeon Yun ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Growth Pattern ◽  
Treatment Strategies ◽  
Preoperative Assessment ◽  
Growth Patterns ◽  
Surrounding Tissue ◽  
Mri Findings ◽  
Predictive Index ◽  
Factors Associated

Soft tissue sarcoma (STS) with an infiltrative histologic growth pattern, when compared to STS with an expansile pattern, may pose difficulties in local control. Preoperative assessment of the presence of infiltrative histologic growth pattern would be helpful in deciding treatment strategies. A review of 144 patients who underwent surgery for extremity STS was performed. Microscopically, the histologic growth pattern was defined as infiltrative if the penetration of the tumor cells into the surrounding tissue was observed. Possible clinicopathologic factors that might be associated with infiltrative histologic growth pattern were investigated with regard to patient demographics, tumor characteristics, and MRI findings. Of the 144 tumors, 71 (49%) showed infiltrative histologic growth pattern. On multivariate analysis, histological subtypes other than liposarcoma (OR = 4.57, p=0.02) and infiltrative border on MRI (OR = 2.48, p=0.01) were independent factors associated with infiltrative histologic growth pattern. Predictive index based on these two factors showed a significant improved accuracy (ROC-AUC = 0.647) for predicting infiltrative histologic growth pattern compared to either factor alone. Our data suggests that liposarcoma histology and tumor border on MRI can predict histologic growth pattern in extremity STS.

scholarly journals PTENSequence Analysis in Endometrial Hyperplasia and Endometrial Carcinoma in Slovak Women

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
H. Gbelcová ◽  
P. Bakeš ◽  
P. Priščáková ◽  
V. Šišovský ◽  
I. Hojsíková ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Endometrial Carcinoma ◽  
Endometrial Hyperplasia ◽  
Female Genital Tract ◽  
Suppressor Gene ◽  
Serous Carcinoma ◽  
Tissue Samples ◽  
Phosphatase And Tensin Homolog ◽  
Coding Regions ◽  
Tensin Homolog

Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree ofPTENalterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions ofPTENgene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

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