scholarly journals Exon 5 of the p53 gene is a target for deletions in ovarian cancer

1998 ◽  
Vol 44 (1) ◽  
pp. 72-77 ◽  
Author(s):  
Katerina Angelopoulou ◽  
Michael A Levesque ◽  
Dionyssios Katsaros ◽  
Rob Shipman ◽  
Eleftherios P Diamandis
Keyword(s):  
Ovarian Cancer ◽  
Human Cancer ◽  
Insertion Site ◽  
Point Mutations ◽  
Pcr Amplification ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Protein Product ◽  
The Other ◽  
Chromosome 17

Abstract Missense point mutations, leading to inactivation of the p53 tumor suppressor gene product, are currently the most frequent alterations in human cancer. Little, however, is known about small intragenic deletions or insertions occurring in this locus of chromosome 17. We have analyzed 56 primary ovarian tumors for the presence of such abnormalities. The analysis was based on multiplex PCR amplification of exons 1 through 11 of the p53 gene and fragment analysis of the generated PCR products. Mutations were detected in 14% (8 of 56) of the tumors. Deletions were much more prevalent than insertions (seven vs one). Six of the deletions and the insertion affected exon 5, and the other deletion was in exon 7. Two deletions and the insertion did not disrupt the reading frame; the protein product was expressed in the tumor at high concentrations in all three cases. The other five deletions generated a frameshift, which is predicted to result in the production of a truncated protein product. In the case of the deletions, a 2–5-bp repeat was present close to the detected deletion, whereas the insertion duplicated the sequence immediately upstream of the insertion site. Overall our findings indicate that small intragenic p53 deletions/insertions are not rare events in ovarian cancer, and that p53 exon 5 is the target in the vast majority (88%) of the cases.

scholarly journals Analysis of the p53 gene by PCR-SSCP in ten cases of Wilms’ tumor

2000 ◽  
Vol 118 (2) ◽  
pp. 49-52 ◽  
Author(s):  
Ricardo Defavery ◽  
José Alexandre Rodrigues Lemos ◽  
Simone Kashima ◽  
José Eduardo Bernardes ◽  
Carlos Alberto Scridelli ◽  
...  
Keyword(s):  
Case Report ◽  
Dna Sequencing ◽  
Wilms Tumor ◽  
Point Mutations ◽  
Low Frequency ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Stage Disease ◽  
Two Samples ◽  
Renal Neoplasia

CONTEXT: Mutations of the p53 tumor suppressor gene are the most frequent alterations observed in human neoplasias affecting adults. In pediatric oncology, however, they have seldom been identified. Wilms’ tumor is a renal neoplasia commonly occurring in children and is associated with mutations of the WT1 gene. The correlation between Wilms’ tumor and alterations of the p53 gene has not been well established, with a low frequency of mutations having been reported in this type of tumor. Mutation may be associated with advanced stage disease and unfavorable histology. OBJECTIVE: To screen for mutations of the p53 gene by the PCR-SSCP method and DNA sequencing in cases of Wilms’ tumor sug-gestive of mutation. DESIGN: Case Report. CASE REPORT: Evaluations of exons 5-9 of the p53 gene in DNA samples extracted by PCR-SSCP from 10 Wilms’ tumors in children at different stages, and DNA sequencing. Changes in SSCP analy-sis were observed in exon 8 in two samples. The probable muta-tions were not confirmed by DNA sequencing. The absence of point mutations in p53 gene observed in the 10 samples of Wilms’ tumor studied agrees with literature data, with DNA sequencing being of fundamental importance for the confirmation of possible mutations.

scholarly journals Detection of p53 mutation and serum monitoring alert caused by Marek’s disease virus in poultry

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Huixia Zhang ◽  
Mengda Liu ◽  
Hui Zhang ◽  
Shengliang Cao ◽  
Yue Li ◽  
...  
Keyword(s):  
Human Cancer ◽  
Point Mutations ◽  
Suppressor Gene ◽  
Marek's Disease ◽  
Economic Losses ◽  
Control Group ◽  
Neoplastic Disease ◽  
Mutant P53 ◽  
Marek’S Disease ◽  
Infected Chicken

Abstract Background Marek’s disease (MD) is a chicken neoplastic disease, which brings huge economic losses to the global poultry industry. The wild type p53, a tumor suppressor gene, plays a key role in blocking cell cycle, promoting apoptosis, and maintaining the stability of the genome. However, the mutant p53 losses its tumor inhibitory role and become an oncogene when a mutation has happened. Results The mutation rate of p53 was 60% in the experimentally and naturally infected chickens. The mutations included point-mutations and deletions, and mostly located in the DNA-binding domain. The mutated p53 was expressed in various tumor tissues in an infected chicken. The mutant P53 proteins were notably accumulated in the cytoplasm due to the loss in the function of nuclear localization. Unlike the study on human cancer, the concentrations of P53 in the serums of MD infected chicken were significantly lower than the control group. Conclusions The p53 mutations were apparent in the development of MD. P53 and P53 antibody level in serum could be a useful marker in the diagnosis and surveillance of MD.

scholarly journals PRKAR1A and Thyroid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3834
Author(s):  
Georgia Pitsava ◽  
Constantine A. Stratakis ◽  
Fabio R. Faucz
Keyword(s):  
Thyroid Cancer ◽  
Molecular Mechanisms ◽  
Chromosomal Rearrangements ◽  
Molecular Genetic ◽  
Point Mutations ◽  
Suppressor Gene ◽  
Chromosome 17 ◽  
Regulatory Subunit ◽  
Thyroid Tumors ◽  
Genetic Ablation

Thyroid cancer is the most common type of endocrine malignancy and the incidence is rapidly increasing. Follicular (FTC) and papillary thyroid (PTC) carcinomas comprise the well-differentiated subtype and they are the two most common thyroid carcinomas. Multiple molecular genetic and epigenetic alterations have been identified in various types of thyroid tumors over the years. Point mutations in BRAF, RAS as well as RET/PTC and PAX8/PPARγ chromosomal rearrangements are common. Thyroid cancer, including both FTC and PTC, has been observed in patients with Carney Complex (CNC), a syndrome that is inherited in an autosomal dominant manner and predisposes to various tumors. CNC is caused by inactivating mutations in the tumor-suppressor gene encoding the cyclic AMP (cAMP)-dependent protein kinase A (PKA) type 1α regulatory subunit (PRKAR1A) mapped in chromosome 17 (17q22–24). Growth of the thyroid is driven by the TSH/cAMP/PKA signaling pathway and it has been shown in mouse models that PKA activation through genetic ablation of the regulatory subunit Prkar1a can cause FTC. In this review, we provide an overview of the molecular mechanisms contributing to thyroid tumorigenesis associated with inactivation of the RRKAR1A gene.

Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines

1990 ◽  
Vol 10 (10) ◽  
pp. 5502-5509
Author(s):  
J Cheng ◽  
M Haas
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Point Mutations ◽  
Leukemia Cell ◽  
P53 Gene ◽  
Suppressor Gene ◽  
T Cell Lines

Human T-cell leukemia and T-cell acute lymphoblastic leukemia cell lines were studied for alterations in the p53 tumor suppressor gene. Southern blot analysis of 10 leukemic T-cell lines revealed no gross genomic deletions or rearrangements. Reverse transcription-polymerase chain reaction analysis of p53 mRNA indicated that all 10 lines produced p53 mRNA of normal size. By direct sequencing of polymerase chain reaction-amplified cDNA, we detected 11 missense and nonsense point mutations in 5 of the 10 leukemic T-cell lines studied. The mutations are primarily located in the evolutionarily highly conserved regions of the p53 gene. One of the five cell lines in which a mutation was detected possesses a homozygous point mutation in both p53 alleles, while the other four cell lines harbor from two to four different point mutations. An allelic study of two of the lines (CEM, A3/Kawa) shows that the two missense mutations found in each line are located on separate alleles, thus both alleles of the p53 gene may have been functionally inactivated by two different point mutations. Since cultured leukemic T-cell lines represent a late, fully tumorigenic stage of leukemic T cells, mutation of both (or more) alleles of the p53 gene may reflect the selection of cells possessing an increasingly tumorigenic phenotype, whether the selection took place in vivo or in vitro. Previously, we have shown that the HSB-2 T-cell acute lymphoblastic leukemia cell line had lost both alleles of the retinoblastoma tumor suppressor gene. Taken together, our data show that at least 6 of 10 leukemic T-cell lines examined may have lost the normal function of a known tumor suppressor gene, suggesting that this class of genes serves a critical role in the generation of fully tumorigenic leukemic T cells.

Mutation of the p53 Gene Is Not a Typical Feature of Hodgkin and Reed-Sternberg Cells in Hodgkin’s Disease

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1755-1760 ◽  
Author(s):  
Manuel Montesinos-Rongen ◽  
Axel Roers ◽  
Ralf Küppers ◽  
Klaus Rajewsky ◽  
Martin-Leo Hansmann
Keyword(s):  
Hodgkin's Disease ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Single Cells ◽  
Point Mutations ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Typical Feature ◽  
P53 Mutations ◽  
Technical Problems

Point mutations of the p53 tumor suppressor gene are a frequent finding in human carcinomas and are thought to be an important oncogenic event. In non-Hodgkin lymphomas, p53 mutations occur in a minor fraction of cases. However, conclusive data are still lacking for Hodgkin’s disease (HD) where the analysis meets technical problems. The neoplastic tumor cell clone in HD is represented by the large Hodgkin and Reed-Sternberg (HRS) cells, which account for only a minority of all cells in the tumor tissue (often <1%). To identify putative HRS cell-specific mutations, single HRS cells were micromanipulated from frozen tissue sections of HD biopsy specimens. Exons 4 to 8 of the p53 gene (in which more than 90% of p53 mutations associated with human neoplasms occur) were amplified from these single cells and sequenced. Mutations of p53 were not found in HRS cells of any of 8 cases of HD analyzed. We conclude that mutation of the p53 gene is only rarely, if at all, involved in the pathogenesis of HD.

Mutation of the p53 Gene Is Not a Typical Feature of Hodgkin and Reed-Sternberg Cells in Hodgkin’s Disease

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1755-1760 ◽  
Author(s):  
Manuel Montesinos-Rongen ◽  
Axel Roers ◽  
Ralf Küppers ◽  
Klaus Rajewsky ◽  
Martin-Leo Hansmann
Keyword(s):  
Hodgkin's Disease ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Single Cells ◽  
Point Mutations ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Typical Feature ◽  
P53 Mutations ◽  
Technical Problems

Abstract Point mutations of the p53 tumor suppressor gene are a frequent finding in human carcinomas and are thought to be an important oncogenic event. In non-Hodgkin lymphomas, p53 mutations occur in a minor fraction of cases. However, conclusive data are still lacking for Hodgkin’s disease (HD) where the analysis meets technical problems. The neoplastic tumor cell clone in HD is represented by the large Hodgkin and Reed-Sternberg (HRS) cells, which account for only a minority of all cells in the tumor tissue (often &lt;1%). To identify putative HRS cell-specific mutations, single HRS cells were micromanipulated from frozen tissue sections of HD biopsy specimens. Exons 4 to 8 of the p53 gene (in which more than 90% of p53 mutations associated with human neoplasms occur) were amplified from these single cells and sequenced. Mutations of p53 were not found in HRS cells of any of 8 cases of HD analyzed. We conclude that mutation of the p53 gene is only rarely, if at all, involved in the pathogenesis of HD.

scholarly journals Mutation status of p53 gene in oral squamous cell carcinoma

2009 ◽  
Vol 56 (4) ◽  
pp. 171-175 ◽  
Author(s):  
Branka Popovic ◽  
Biljana Jekic ◽  
Drago Jelovac ◽  
Ivana Novakovic
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Point Mutation ◽  
Squamous Cell ◽  
Cell Cycle Control ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Protein Product

Introduction. p53 gene is the most common tumor suppressor gene involved in pathogenesis oral squamous cell carcinoma (OSCC). Protein product of p53 gene contributes to cell cycle control and apoptosis. p53 gene mutations may lead to uncontrolled cell growth. The aim of this study was to determine the incidence of mutation in DNA-binding domain of p53 gene. Materials and Methods. In the 60 specimens, the presence of point mutation in exons 5, 6, 7 and 8 was detected using PCR-SSCP method. To confirm the presence of p53 mutation found by SSCP method, five samples were analyzed by sequencing of exon 5. Results. Point mutation affecting exons 5, 6, 7 and 8 were found in 60% of analyzed samples. A higher incidence of mutation was detected in exon 7 and 8 (60%), than in exon 5 and 6. Sequencing of exon 5, confirmed the presence of mutations revealed by SSCP method. Study of associations showed an increase of p53 mutations in poor differentiated and carcinoma of higher clinical stages. Conclusion. p53 gene is one of major factor in control of cell cycle and has important role in pathogenesis of oral squamous cell carcinoma.

scholarly journals p53 mutations as fingerprints of environmental carcinogens

2000 ◽  
Vol 72 (6) ◽  
pp. 995-999 ◽  
Author(s):  
Rengul Cetin-Atalay ◽  
Mehmet Ozturk
Keyword(s):  
Great Majority ◽  
P53 Gene ◽  
Suppressor Gene ◽  
Protein Product ◽  
P53 Mutation ◽  
P53 Mutations ◽  
Environmental Carcinogens ◽  
Molecular Fingerprints ◽  
Human Cancers ◽  
Mutation Spectra

Mutations of the p53 tumor suppressor gene occur in a great majority of human cancers. The protein product of p53 gene is involved in DNA damage response. Consequently, p53 gene may be a preferred target for environmental carcinogens, which also act as DNA-damaging agents. This is probably why p53 mutations are frequent in cancers linked to environmental carcinogens. Moreover, these carcinogens leave molecular fingerprints on the p53 gene. Thus, the study of p53 mutation spectra has been a useful approach to implicate suspected carcinogens to different human cancers. This review provides further insight into the significance of p53 mutation spectra in ten common human malignancies (skin, liver, lung, bladder, breast, head and neck, esophagus, stomach and colorectal cancers, and hematological malignancies), in relation with environmental carcinogens.

scholarly journals Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines.

1990 ◽  
Vol 10 (10) ◽  
pp. 5502-5509 ◽  
Author(s):  
J Cheng ◽  
M Haas
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Cell Lines ◽  
Lymphoblastic Leukemia ◽  
Point Mutations ◽  
Leukemia Cell ◽  
P53 Gene ◽  
Suppressor Gene ◽  
T Cell Lines

Human T-cell leukemia and T-cell acute lymphoblastic leukemia cell lines were studied for alterations in the p53 tumor suppressor gene. Southern blot analysis of 10 leukemic T-cell lines revealed no gross genomic deletions or rearrangements. Reverse transcription-polymerase chain reaction analysis of p53 mRNA indicated that all 10 lines produced p53 mRNA of normal size. By direct sequencing of polymerase chain reaction-amplified cDNA, we detected 11 missense and nonsense point mutations in 5 of the 10 leukemic T-cell lines studied. The mutations are primarily located in the evolutionarily highly conserved regions of the p53 gene. One of the five cell lines in which a mutation was detected possesses a homozygous point mutation in both p53 alleles, while the other four cell lines harbor from two to four different point mutations. An allelic study of two of the lines (CEM, A3/Kawa) shows that the two missense mutations found in each line are located on separate alleles, thus both alleles of the p53 gene may have been functionally inactivated by two different point mutations. Since cultured leukemic T-cell lines represent a late, fully tumorigenic stage of leukemic T cells, mutation of both (or more) alleles of the p53 gene may reflect the selection of cells possessing an increasingly tumorigenic phenotype, whether the selection took place in vivo or in vitro. Previously, we have shown that the HSB-2 T-cell acute lymphoblastic leukemia cell line had lost both alleles of the retinoblastoma tumor suppressor gene. Taken together, our data show that at least 6 of 10 leukemic T-cell lines examined may have lost the normal function of a known tumor suppressor gene, suggesting that this class of genes serves a critical role in the generation of fully tumorigenic leukemic T cells.

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