scholarly journals Detection and Correlation of Single and Concomitant TP53, PTEN, and CDKN2A Alterations in Gliomas

2019 ◽  
Vol 20 (11) ◽  
pp. 2658 ◽  
Author(s):  
Igor Andrade Pessôa ◽  
Carolina Koury Amorim ◽  
Wallax Augusto Silva Ferreira ◽  
Fernanda Sagica ◽  
José Reginaldo Brito ◽  
...  
Keyword(s):  
Tumor Suppressor Genes ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Low Grade ◽  
Heterozygous Deletion ◽  
Single Strand Conformational Polymorphism ◽  
Primary Tumors ◽  
Tumor Subtypes ◽  
Frequent Event

Gliomas are the most frequent primary tumors of central nervous system and represent a heterogeneous group of tumors that originates from the glial cells. TP53, PTEN, and CDKN2A are important tumor suppressor genes that encode proteins involved in sustaining cellular homeostasis by different signaling pathways. Though genetic alterations in these genes play a significant role in tumorigenesis, few studies are available regarding the incidence and relation of concomitant TP53, PTEN, and CDKN2A alterations in gliomas. The purpose of this study was to evaluate the occurrence of mutation and deletion in these genes, through single-strand conformational polymorphism, array-comparative genomic hybridization, and fluorescence in situ hybridization techniques, in 69 gliomas samples. Molecular results demonstrated a significant higher prevalence of TP53, PTEN, and CDKN2A alterations in astrocytoma than other tumor subtypes, and heterozygous deletion was the most frequent event. In addition, a significant association was observed between TP53 and CDKN2A alterations (p = 0.0424), which tend to coexist in low grade astrocytomas (5/46 cases (10.9%)), suggesting that they are early events in development of these tumors, and PTEN and CDKN2A deletions (p = 0.0022), which occurred concomitantly in 9/50 (18%) patients, with CDKN2A changes preceding PTEN deletions, present preferably in high-grade gliomas.

Genetic alterations in a papillary glioneuronal tumor

2008 ◽  
Vol 1 (1) ◽  
pp. 99-102 ◽  
Author(s):  
Claudia Faria ◽  
José Miguéns ◽  
João Lobo Antunes ◽  
Cândida Barroso ◽  
José Pimentel ◽  
...  
Keyword(s):  
Genetic Alterations ◽  
Point Of View ◽  
Chromosome 7 ◽  
Glioneuronal Tumor ◽  
Comparative Genomic ◽  
Low Grade ◽  
The Central Nervous System ◽  
High Level ◽  
Glioneuronal Tumors

✓Papillary glioneuronal tumors (PGNTs) are rare lesions of the central nervous system, and no information exists on the genetic alterations in these neoplasms. The authors report on such a case in a child. Genetic studies revealed that the tumor was characterized by gains and structural alterations involving only chromosome 7 with breakpoints at 7p22. By using comparative genomic hybridization, the authors observed a high-level amplification region at 7p14~q12. Fluorescence in situ hybridization with a probe for EGFR revealed that this gene was not amplified. Similar to other patients with PGNTs, the patient in the present case fared well. From a genetic point of view the data in the present case are in accordance with previous findings of EGFR amplifications as uncommon in low-grade gliomas and gangliogliomas. Recurrent rearrangements of chromosome 7 have been noted in other mixed glioneuronal tumors. The data in this case suggest that genes located at chromosome 7 can also be involved in the pathogenesis of PGNT. In clinical terms it will be especially important to corroborate, through the analysis of further cases, the involvement of the chromosome 7p22 locus, a region where glial and neuronal linked genes (RAC1 and NXPH1) are known to be located.

scholarly journals A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Sarah Hackman ◽  
Richard D. Hammer ◽  
Lester Layfield
Keyword(s):  
Abdominal Cavity ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Small Cell ◽  
Comparative Genomic ◽  
Cell Nuclei ◽  
Pleural Tumor ◽  
Young Males ◽  
Round Cell Tumors

Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs) which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22)(p13;q12) translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22)(p13;q12) translocation disclosed loss of theEWSR1gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH) confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of theEWSR1andWT1gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

Comprehensive Genome-Wide Profile of Regional Gains and Losses in Multiple Myeloma Using Array-CGH: The 1q21 Amplification and Potential Role of the BCL-9 Gene in Multiple Myeloma Pathogenesis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 785-785 ◽  
Author(s):  
Ruben Carrasco ◽  
Giovanni Tonon ◽  
Cameron Brennan ◽  
Alexei Protopopov ◽  
Raktim Sinha ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Copy Number ◽  
Structural Changes ◽  
Array Cgh ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Primary Tumors ◽  
Gains And Losses

Abstract Multiple Myeloma (MM) is characterized by a clonal proliferation of abnormal plasma cells in the bone marrow and is among the most frequent and lethal hematological diseases. In spite of significant effort towards the identification of the molecular events leading to this malignancy, the genetic alterations responsible for the pathogenesis of this disease remain poorly understood. Regional copy number alterations (CNAs) in cancer genomes have been among the most informative structural changes in cancer and have led to the discovery of many oncogenes and tumor supressor genes. Using array comparative genomic hybridization (array-CGH) and expression microarray technologies we have analyzed a large collection of cell lines and clinically annotated primary tumors. This high-resolution genomic analysis has identified all previously reported regional gains and losses as well as many novel highly recurrent genetic loci with potential biological and clinical relevance. In particular, we have identified an amplification at chromosome 1q21 as one of the most recurrent genetic changes in cell lines and in a subgroup of primary tumors. This chromosomal change has been previously implicated with disease progression. Analysis across several cell lines has allowed the identification of a Minimal Common Region (MCRs) of amplification at 1q21. Correlation between DNA copy number changes and expression profiling data has identified a limited set of candidate genes within this MCR that are amplified and overexpressed. Using shRNAi technology we have identified BCL-9 as a candidate gene residing at the 1q21 MCR. In vitro and in vivo functional data about the role of BL-9 will be presented. These data will provide critical understanding on the diverse pathways leading to Multiple Myeloma progression.

scholarly journals Genetic Alterations in Presumptive Precursor Lesions of Breast Carcinomas

2002 ◽  
Vol 24 (2-3) ◽  
pp. 69-76 ◽  
Author(s):  
Michaela Aubele ◽  
Martin Werner ◽  
Heinz Höfler
Keyword(s):  
Ductal Carcinoma ◽  
Early Stage ◽  
Dna Amplification ◽  
Genetic Alterations ◽  
Molecular Genetic Analysis ◽  
Premalignant Lesions ◽  
Comparative Genomic ◽  
Precursor Lesions ◽  
Normal Epithelium

The hypothetical multistep model of breast carcinogenesis suggests a transition from normal epithelium to invasive carcinoma via intraductal hyperplasia (without and with atypia) andin situcarcinoma. These presumptive precursor lesions are currently defined by their histological features, and their prognosis is imprecisely estimated from indirect epidemiological evidence. Cytogenetic and molecular‐genetic analysis of these lesions give evidence for an accumulation of various genetic alterations during breast tumorigenesis. Using immuno‐histochemistry overexpression of the c‐erbB‐2 oncogene was found in ductal carcinomain situ(DCIS), but not in atypical intraductal hyperplasia (AIDH) and intraductal hyperplasia (IDH). An expression of mutant p53 tumor suppressor gene as well as expression of cyclin D1 was identified in DCIS. In IDH lesions loss of heterozygosity (LOH) at various loci could be identified, and comparative genomic hybridization (CGH) and fluorescencein situhybridization (FISH) studies delivered evidence for DNA amplification on chromosomal region 20q13 in the early stage of IDH. However, little is currently known about genetic alterations in those premalignant lesions, and the chronology of genetic alterations and histopathological changes during carcinogenesis is mainly undiscovered. Figure 1 can be viewed in colour onhttp://www.esacp.org/acp/2002/24‐23/aubele.htm

Genomic Imbalances Are Associated with Outcome of Helicobacter pylori Eradication in t(11;18)(q21;q21)-Negative Gastric MALT Lymphomas.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2424-2424 ◽  
Author(s):  
Noriko Fukuhara ◽  
Hiroyuki Tagawa ◽  
Tsuneya Nakamura ◽  
Hiroshi Inagaki ◽  
Yasuo Morishima ◽  
...  
Keyword(s):  
Malt Lymphoma ◽  
Locally Advanced ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Aggressive Lymphoma ◽  
Comparative Genomic ◽  
Low Grade ◽  
Independent Group ◽  
Genomic Imbalances ◽  
H Pylori

Abstract Background: Approximately 70% of low grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma cases are successfully treated by H. pylori eradication. The MALT lymphoma resistant to this therapy needs an additional therapy. A part of the tumors transform to an aggressive lymphoma including diffuse large B-cell lymphoma (DLBCL). The t(11;18)(q21;q21) characteristic to MALT lymphoma is recognized as a marker for H. pylori independency, but this marker is found in only a half of the MALT lymphomas resistant to H. pylori eradication. Therefore the detailed genomic features of eradication resistant group as well as dependent group are needed to understand molecular basis. Patients and Methods: We performed array-based comparative genomic hybridization for 30 gastric MALT lymphomas treated with H. pylori eradication. These included 10 cases of t(11;18)(q21;q21)-positive MALT group, 10 cases of t(11;18)(q21;q21)-negative MALT with H. pylori dependent group and 10 cases of t(11;18)(q21;q21)-negative MALT with H. pylori independent group. The presence of t(11;18)(q21;q21) was identified by a multiplex reverse transcriptase polymerase chain reaction of the API2-MALT1 chimeric transcript. Results: Almost no significant genetic alterations were found in t(11;18)(q21;q21)-positive MALT lymphoma, whereas numerous genomic alterations were found in those without t(11;18)(q21;q21). These aberrations were mostly similar to those found in DLBCL (Tagawa et al., Blood 106:5, 2005). Trisomy 3 is most recurrent and 7q loss specific to SMZL is also recurrent. Within the t(11;18)(q21;q21)-negative MALT lymphoma group, presence of genomic imbalances is more frequent in H. pylori independent group (one of ten (10%) vs seven of ten (70%); p =0.019, two-sided fisher’s exact test). Neither locally advanced disease nor including large cell component is correlated with H. pylori independency, respectively. Conclusions: Genomic imbalances are associated with H. pylori independency in t(11;18)(q21;q21)-negative gastric MALT lymphomas. Thus, the genomic imbalances may have a role in the acquisition of H. pylori-independent growth.

Pediatric brain tumors: genetics and clinical outcome

2010 ◽  
Vol 5 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Claudia Faria ◽  
José Miguéns ◽  
João Lobo Antunes ◽  
Duarte Salgado ◽  
Sofia Nunes ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Clinical Outcome ◽  
Comparative Genomic Hybridization ◽  
Poor Prognosis ◽  
Progressive Disease ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Low Grade ◽  
High Grade ◽  
Genomic Hybridization

Object In this paper the authors' goal was to investigate the genetic characteristics of primary brain tumors in children and determine their influence on clinical outcome. Methods The authors performed high-resolution comparative genomic hybridization studies in 14 low-grade and 12 high-grade brain neoplasms in 26 children who underwent surgery between 2005 and 2007. Results Complex comparative genomic hybridization alterations were observed in 2 (14.3%) of the 14 lowgrade lesions and in 8 (66.6%) of the 12 high-grade lesions. High-level amplifications of DNA were detected in 3 cases, namely in a desmoplastic medulloblastoma where a c-Myc amplification was found. Gains of 1q were detected in 2 low-grade and 6 high-grade lesions that were classified as ependymomas, astrocytomas, oligodendrogliomas, oligoastrocytomas, and gangliogliomas. When the authors correlated genetics with outcome, they noted that among the low-grade neoplasms only the 2 patients who presented with complex comparative genomic hybridization alterations had to undergo reoperation because of recurrent disease. The patient with c-Myc amplification died of progressive disease. Gains of 1q were only observed in tumor cases with progressive disease. Conclusions Complex genetic alterations are indicative of a less favorable outcome in low-grade tumors. In these cases, closer follow-up should be pursued. The authors corroborate that c-Myc amplification is a marker of poor prognosis in medulloblastomas. In this study, they were able to verify that a 1q gain correlates with a poor clinical outcome, independent of tumor grade and histological type. The authors propose that it may be considered a common marker of poor prognosis in these neoplasms.

GENETIC ALTERATIONS IN CARCINOMAS IN SITU OF THE BLADDER BY COMPARATIVE GENOMIC HYBRIDIZATION

1999 ◽  
pp. 117
Author(s):  
Regina M. Hovey ◽  
Lynn Bjerke ◽  
Lucy Epstein ◽  
Michael Muscheck ◽  
Vivek Barghava ◽  
...  
Keyword(s):  
Comparative Genomic Hybridization ◽  
Genetic Alterations ◽  
Comparative Genomic ◽  
Genomic Hybridization

High performance Nanogold™-in situ hybridzation and its use in the detection of hybridized and PCR-amplified microscopical preparations

1996 ◽  
Vol 54 ◽  
pp. 896-897
Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Messenger Rna ◽  
High Performance ◽  
Detection System ◽  
Direct Methods ◽  
Genetic Alterations ◽  
Chain Reaction ◽  
Protein Encoding ◽  
Polymerase Chain

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.

scholarly journals Intra-Cystic (In Situ) Mucoepidermoid Carcinoma: A Clinico-Pathological Study of 14 Cases

2020 ◽  
Vol 9 (4) ◽  
pp. 1157
Author(s):  
Saverio Capodiferro ◽  
Giuseppe Ingravallo ◽  
Luisa Limongelli ◽  
Mauro Mastropasqua ◽  
Angela Tempesta ◽  
...  
Keyword(s):  
Alcian Blue ◽  
Tumor Invasion ◽  
Conservative Surgery ◽  
Low Grade ◽  
Mucin Production ◽  
Cystic Component ◽  
Early Growth Phase ◽  
Hematoxylin Eosin

Aims: To report on the clinico-pathological features of a series of 14 intra-oral mucoepidermoid carcinomas showing exclusive intra-cystic growth. Materials and methods: All mucoepidermoid carcinomas diagnosed in the period 1990–2012 were retrieved; the original histological preparations were reviewed to confirm the diagnosis and from selected cases, showing exclusive intra-cystic neoplastic components, additional sections were cut at three subsequent 200 m intervals and stained with Hematoxylin–Eosin, PAS, Mucicarmine and Alcian Blue, to possibly identify tumor invasion of the adjacent tissues, which could have been overlooked in the original histological preparations. Additionally, pertinent findings collected from the clinical charts and follow-up data were analyzed. Results: We identified 14 intraoral mucoepidermoid carcinomas treated by conservative surgery and with a minimum follow up of five years. The neoplasms were located in the hard palate (nine cases), the soft palate (two), the cheek (two) and the retromolar trigone (one). In all instances, histological examination revealed the presence of a single cystic space, containing clusters of columnar, intermediate, epidermoid, clear and mucous-producing cells, the latter exhibiting distinct intra-cytoplasmic mucin production, as confirmed by PAS, Mucicarmine and Alcian Blue stains. The cysts were entirely circumscribed by fibrous connective tissue, and no solid areas or infiltrating tumor cell clusters were detected. Conservative surgical resection was performed in all cases, and no recurrences or nodal metastases were observed during follow up. Conclusions: Mucoepidermoid carcinomas showing prominent (>20%) intra-cystic proliferation currently are considered low-grade tumors. In addition, we also unveil the possibility that mucoepidermoid carcinomas, at least in their early growth phase, may display an exclusive intra-cystic component and might be considered as in situ carcinomas, unable to infiltrate adjacent tissues and metastasize.

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