Molecular genetic analysis of phosphatase and tensin homolog and p16 tumor suppressor genes in patients with malignant glioma

2003 ◽  
Vol 14 (4) ◽  
pp. 1-7 ◽  
Author(s):  
Jafri Malin Abdullah ◽  
Norafiza Zainuddin ◽  
Sarina Sulong ◽  
Hasnan Jaafar ◽  
Mohamad Nizam Isa
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Molecular Genetic ◽  
Malignant Gliomas ◽  
Point Mutations ◽  
Molecular Genetic Analysis ◽  
Chromosome 10 ◽  
Suppressor Genes ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog

Object Several genes have been shown to carry mutations in human malignant gliomas, including the phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and p16 tumor suppressor genes. Alterations of this gene located on chromosome 10 q23 and 9p21, respectively, may contribute to gliomagenesis. In this study, the authors analyzed 20 cases of malignant gliomas obtained in patients living on the east coast of Malaysia to investigate the possibilities of involvement of the PTEN and p16 genes. Methods Samples of DNA were amplified by polymerase chain reaction (PCR), analyzed by single-stranded conformation polymorphism (SSCP), and subsequently by sequencing. Two cases of glioblastoma multiforme, three cases of anaplastic astrocytoma, one case of anaplastic pleomorphic xanthoastrocytoma, and one case of anaplastic ependymoma showed SSCP band shifts in PTEN mutational analyses. The DNA sequencing analyses of these samples revealed missense and nonsense mutations, with cluster of mutations in the region 5' to the core phosphatase motif of exon 5 and the 5'-end of exon 6. No abnormal migration shifts were detected in the glioma samples analyzed for point mutations of the p16 gene. Homozygous deletions of p16 were also not detected in all samples. Conclusions These findings indicate that mutations of the PTEN genes were likely to contribute to the tumorigenesis and morphological transformations of gliomas. In addition, the alterations of the p16 gene might not play a major role in tumorigenesis of malignant gliomas in Malaysian patients.

Analysis of loss of heterozygosity on chromosomes 10q, 11, and 16 in medulloblastomas

2001 ◽  
Vol 94 (5) ◽  
pp. 799-805 ◽  
Author(s):  
Xiao-lu Yin ◽  
Jesse C. Pang ◽  
Yan-hui Liu ◽  
Edith Y. Chong ◽  
Yue Cheng ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Loss Of Heterozygosity ◽  
Tumor Suppressor Genes ◽  
Molecular Genetic ◽  
Genetic Material ◽  
Suppressor Genes ◽  
Blood Samples ◽  
Content Type ◽  
Targeted Deletion ◽  
Fine Print

Object. The loss of genetic material from specific chromosome loci is a common feature in the oncogenesis of tumors and is often indicative of the presence of important tumor suppressor genes at these loci. Recent molecular genetic analyses have demonstrated frequent loss of chromosomes 10q, 11, and 16 in medulloblastomas. The aim of this study was to localize the targeted deletion regions on the three aforementioned chromosomes in medulloblastomas. Methods. Loss of heterozygosity (LOH) was examined on chromosomes 10q, 11, and 16 in a series of 22 primary and two recurrent medulloblastomas by using polymerase chain reaction—based microsatellite analysis. The DNA extracted from the tumors and corresponding normal blood samples were amplified independently in the presence of radioactively labeled microsatellite primers, resolved by denaturing gel electrophoresis and processed for autoradiography. The DNA obtained from control blood samples that displayed allelic heterozygosity at a given microsatellite locus were considered informative. Loss of heterozygosity was inferred when the allelic signal intensity of the tumor sample was reduced by at least 40%, relative to that of the constitutional control. The LOH analysis demonstrated that deletions of chromosomes 10q, 11p, and 16q are recurrent genetic events in the development of medulloblastomas. Three subchromosomal regions of loss have been identified and are localized to the deleted in malignant brain tumors 1 [DMBT1] gene site on chromosomes 10q25, 11p13–11p15.1, and 16q24.1–24.3. Conclusions. These results indicate that DMBT1 is closely associated with the oncogenesis of medulloblastomas and highlight regions of loss on chromosomes 11p and 16q for further fine mapping and cloning of candidate tumor suppressor genes that are important for the genesis of medulloblastoma.

scholarly journals Structural and functional evidence for the presence of tumor suppressor genes on the short arm of chromosome 10 in human gliomas

Oncogene ◽  
1998 ◽  
Vol 16 (2) ◽  
pp. 257-263 ◽  
Author(s):  
Hiroyuki Kon ◽  
Yukihiko Sonoda ◽  
Toshihiro Kumabe ◽  
Takashi Yoshimoto ◽  
Takao Sekiya ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Human Gliomas ◽  
Chromosome 10 ◽  
Suppressor Genes

Molecular Pathogenesis of MDS

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 156-160 ◽  
Author(s):  
A. Thomas Look
Keyword(s):  
Tumor Suppressor ◽  
Progenitor Cells ◽  
Tumor Suppressors ◽  
Tumor Suppressor Genes ◽  
Molecular Mechanisms ◽  
Point Mutations ◽  
Suppressor Genes ◽  
Hematopoietic Stem ◽  
Chromosomal Deletions ◽  
Genes Encoding

Abstract Clonal disorders of hematopoiesis, such as myelodysplastic syndromes (MDS) and myeloproliferative diseases (MPD), affect both hematopoietic stem cells and progenitor cells within the erythroid, platelet and granulocytic lineages and can have devastating consequences in children and adults. The genetic features of these diseases often include clonal, nonrandom chromosomal deletions (e.g., 7q–, 5q–, 20q–, 6q–, 11q– and 13q–) that appear to inactivate tumor suppressor genes required for the normal development of myeloid cells (reviewed in Bench1 and Fenaux2). These putative tumor suppressors have proved to be much more difficult to identify than oncogenes activated by chromosomal translocations, the other major class of chromosomal lesions in MDS and MPD.3 Although MDS and MPD are almost certainly caused by mutations in stem/progenitor cells,4 the role of inactivated tumor suppressor genes in this process remains poorly understood. In a small portion of myeloid diseases, mutations have been identified in genes encoding factors known to be required for normal hematopoiesis, such as PU.1, RUNX1, CTNNA1 (α-catenin) and c/EBPα, and implicating these genes as tumor suppressors.5–7 Nonetheless, the identities of most deletion-associated tumor suppressors in these diseases remains elusive, despite complete sequencing of the human genome. The deleted regions detected by cytogenetic methods are generally very large, containing many hundreds of genes, thus making it hard to locate the critical affected gene or genes. It is also unclear whether dysfunctional myelopoiesis results from haploinsufficiency, associated with the deletion of one allele, or from homozygous inactivation due to additional point mutations or microdeletions of the retained wild-type allele. In general MDS have proved surprisingly resistant to conventional treatments. Targeted therapeutic advances in MDS will likely depend on a full comprehension of underlying molecular mechanisms, in particular the tumor suppressor genes lost through clonal, nonrandom chromosomal deletions, such as the 7q– and (del)5q.

scholarly journals Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor

2021 ◽  
Vol 12 ◽  
Author(s):  
Tianyu He ◽  
Xiaoyun Zhang ◽  
Jianyu Hao ◽  
Shigang Ding
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Malignant Tumors ◽  
Biological Effects ◽  
Pten Protein ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Lipid Phosphatase ◽  
And Migration

The Phosphatase and tensin homolog (PTEN) gene is one of the most important tumor suppressor genes, which acts through its unique protein phosphatase and lipid phosphatase activity. PTEN protein is widely distributed and exhibits complex biological functions and regulatory modes. It is involved in the regulation of cell morphology, proliferation, differentiation, adhesion, and migration through a variety of signaling pathways. The role of PTEN in malignant tumors of the digestive system is well documented. Recent studies have indicated that PTEN may be closely related to many other benign processes in digestive organs. Emerging evidence suggests that PTEN is a potential therapeutic target in the context of several non-neoplastic diseases of the digestive tract. The recent discovery of PTEN isoforms is expected to help unravel more biological effects of PTEN in non-neoplastic digestive diseases.

Expression of the Tumor Suppressor Genes NF2, 4.1B, and TSLC1 in Canine Meningiomas

2009 ◽  
Vol 46 (5) ◽  
pp. 884-892 ◽  
Author(s):  
P. J. Dickinson ◽  
E. I. Surace ◽  
M. Cambell ◽  
R. J. Higgins ◽  
C. M. Leutenegger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor ◽  
Western Blotting ◽  
Tumor Suppressor Genes ◽  
Molecular Genetic ◽  
Tumor Grade ◽  
Suppressor Gene ◽  
Early Event ◽  
Rt Pcr ◽  
Suppressor Genes

Meningiomas are common primary brain tumors in dogs; however, little is known about the molecular genetic mechanisms involved in their tumorigenesis. Several tumor suppressor genes have been implicated in meningioma pathogenesis in humans, including the neurofibromatosis 2 ( NF2), protein 4.1B ( 4.1 B), and tumor suppressor in lung cancer-1 ( TSLC1) genes. We investigated the expression of these tumor suppressor genes in a series of spontaneous canine meningiomas using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) ( NF2; n = 25) and western blotting (NF2/merlin, 4.1B, TSLC1; n = 30). Decreased expression of 4.1B and TSLC1 expression on western blotting was seen in 6/30 (20%) and in 15/30 (50%) tumors, respectively, with 18/30 (60%) of meningiomas having decreased or absent expression of one or both proteins. NF2 gene expression assessed by western blotting and RT-PCR varied considerably between individual tumors. Complete loss of NF2 protein on western blotting was not seen, unlike 4.1B and TSLC1. Incidence of TSLC1 abnormalities was similar to that seen in human meningiomas, while perturbation of NF2 and 4.1B appeared to be less common than reported for human tumors. No association was observed between tumor grade, subtype, or location and tumor suppressor gene expression based on western blot or RT-PCR. These results suggest that loss of these tumor suppressor genes is a frequent occurrence in canine meningiomas and may be an early event in tumorigenesis in some cases. In addition, it is likely that other, as yet unidentified, genes play an important role in canine meningioma formation and growth.

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