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 Abnormal expression of the p53-binding protein MDM2 in Hodgkin's disease

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4295-4300 ◽  
Author(s):  
M Chilosi ◽  
C Doglioni ◽  
F Menestrina ◽  
L Montagna ◽  
A Rigo ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Molecular Mechanisms ◽  
Hodgkin’S Disease ◽  
P53 Protein ◽  
P53 Gene ◽  
Antigen Expression ◽  
Suppressor Gene ◽  
Epstein Barr Virus Infection ◽  
Marker Combination ◽  
Abnormal Accumulation

The possible involvement of p53 tumor suppressor gene in the pathogenesis of Hodgkin's disease (HD) is suggested by the frequent finding of abnormal accumulation of p53 protein in the nuclei of Reed- Sternberg cells and their variants (H-RS) in a large proportion of cases. This finding, besides being consistent with the presence of p53 gene mutations, might represent a consequence of the inactivating interaction between p53 and p53-binding proteins such as the product of the MDM2 cellular oncogene. We have examined an unselected series of 77 HD cases of different histologic patterns for the expression of p53 and MDM2 proteins, using specific monoclonal antibodies and sensitive immunohistochemical techniques in single- and double-marker combination. In the large majority of cases (66/77), a variable proportion of H-RS cells expressed MDM2 that was strictly confined to the nuclei. Coexpression of both MDM2 and p53 was common in the same cells. The abnormal nuclear expression of p53 and MDM2 did not seem to correlate with the presence of Epstein-Barr virus infection, as shown by the results of LMP-1 antigen expression and EBER in situ hybridization analysis. Our data suggest that the abnormal accumulation of MDM2 and p53 proteins in HD might reflect a derangement of molecular mechanisms that could play a pathogenetic role in this disease.

scholarly journals Persistence of the same viral strain in early and late relapses of Epstein-Barr virus-associated Hodgkin's disease

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2447-2451 ◽  
Author(s):  
P Brousset ◽  
D Schlaifer ◽  
F Meggetto ◽  
E Bachmann ◽  
S Rothenberger ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Receptor Gene ◽  
Point Mutations ◽  
Viral Strain ◽  
Barr Virus ◽  
First Case ◽  
Epstein Barr

Twelve cases of relapsing Hodgkin's disease were investigated for the presence of Epstein-Barr virus (EBV). Of these, 7 cases contained EBV gene products (LMP1, EBER RNA) in the diagnostic Reed-Sternberg cells and variants at first presentation and at relapse(s), whereas 5 cases were negative at both first diagnosis and relapse. Among the 7 EBV- positive cases, material for DNA extraction was available in 2 cases at both diagnosis and relapse(s). Ig and T-cell receptor gene rearrangements displayed a germline configuration in the 2 cases. However, Southern blot analysis of the terminal repeats (TR) of EBV genome showed that, in 1 of the 2 cases, the fragment was of the same size at diagnosis and in the subsequent two relapses (1 early and 1 late). The second case contained monoclonal EBV genome at diagnosis, but the Southern analysis of the TR was negative at relapse. The latent membrane protein (LMP1) sequence analysis confirmed the persistence of a distinctive viral strain in each of the 2 cases with individual abnormalities within the carboxy terminal region (5 point mutations and a 30-bp deletion for the first case and 6 point mutations for the second case). The persistence of a given strain in early and late relapses is evidence towards the view that in Hodgkin's disease such relapses are related to a single residual tumor cell clone.

scholarly journals Persistence of the same viral strain in early and late relapses of Epstein-Barr virus-associated Hodgkin's disease

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2447-2451 ◽  
Author(s):  
P Brousset ◽  
D Schlaifer ◽  
F Meggetto ◽  
E Bachmann ◽  
S Rothenberger ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Receptor Gene ◽  
Point Mutations ◽  
Viral Strain ◽  
Barr Virus ◽  
First Case ◽  
Epstein Barr

Abstract Twelve cases of relapsing Hodgkin's disease were investigated for the presence of Epstein-Barr virus (EBV). Of these, 7 cases contained EBV gene products (LMP1, EBER RNA) in the diagnostic Reed-Sternberg cells and variants at first presentation and at relapse(s), whereas 5 cases were negative at both first diagnosis and relapse. Among the 7 EBV- positive cases, material for DNA extraction was available in 2 cases at both diagnosis and relapse(s). Ig and T-cell receptor gene rearrangements displayed a germline configuration in the 2 cases. However, Southern blot analysis of the terminal repeats (TR) of EBV genome showed that, in 1 of the 2 cases, the fragment was of the same size at diagnosis and in the subsequent two relapses (1 early and 1 late). The second case contained monoclonal EBV genome at diagnosis, but the Southern analysis of the TR was negative at relapse. The latent membrane protein (LMP1) sequence analysis confirmed the persistence of a distinctive viral strain in each of the 2 cases with individual abnormalities within the carboxy terminal region (5 point mutations and a 30-bp deletion for the first case and 6 point mutations for the second case). The persistence of a given strain in early and late relapses is evidence towards the view that in Hodgkin's disease such relapses are related to a single residual tumor cell clone.

Hodgkin's Disease, Lymphomatoid Papulosis, and Cutaneous T-Cell Lymphoma Derived from a Common T-Cell Clone

1992 ◽  
Vol 326 (17) ◽  
pp. 1115-1122 ◽  
Author(s):  
Thomas H. Davis ◽  
Cynthia C. Morton ◽  
Robert Miller-Cassman ◽  
Steven P. Balk ◽  
Marshall E. Kadin
Keyword(s):  
T Cell ◽  
Hodgkin's Disease ◽  
Cell Lymphoma ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Lymphomatoid Papulosis ◽  
T Cell Clone

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 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.

Hodgkin/Reed-Sternberg Cells Induce Fibroblasts to Secrete Eotaxin, a Potent Chemoattractant for T Cells and Eosinophils

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 2065-2071 ◽  
Author(s):  
Franziska Jundt ◽  
Ioannis Anagnostopoulos ◽  
Kurt Bommert ◽  
Florian Emmerich ◽  
Gerd Müller ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Neutralizing Antibodies ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
Allergic Inflammation ◽  
Dermal Fibroblasts ◽  
Th2 Cells ◽  
T Helper 2 ◽  
Th2 Cell ◽  
Necrosis Factor

Hodgkin’s disease is histopathologically characterized by the relative scarcity of neoplastic Hodgkin and Reed-Sternberg cells and for yet unknown reasons by an abundant reactive background of T lymphocytes and often eosinophils. Eotaxin is a CC-chemokine attracting eosinophils and T helper 2 (Th2) cells in allergic inflammation. We now report that eotaxin is strongly expressed in fibroblasts of Hodgkin’s disease tissues, whereas Hodgkin/Reed-Sternberg cells do not express this chemokine. In tissue culture, Hodgkin’s disease tumor cells induce eotaxin expression in cocultured dermal fibroblasts in a concentration leading to a specific chemotactic response of a Th2 cell clone. Production of tumor necrosis factor- (TNF-) by Hodgkin/Reed-Sternberg cells appears to be responsible for this induction, because blocking of TNF- by neutralizing antibodies prevented fibroblast eotaxin expression. Our data suggest that eotaxin is involved in the pathobiology of Hodgkin’s disease by contributing to eosinophil and T-lymphocyte recruitment.

scholarly journals Single-Cell Analysis of the t(14;18)(q32;q21) Chromosomal Translocation in Hodgkin's Disease Demonstrates the Absence of This Translocation in Neoplastic Hodgkin and Reed-Sternberg Cells

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2866-2874 ◽  
Author(s):  
Sylvia Gravel ◽  
Georges Delsol ◽  
Talal Al Saati
Keyword(s):  
Lymph Nodes ◽  
Single Cell ◽  
Hodgkin's Disease ◽  
Single Cell Analysis ◽  
Hodgkin’S Disease ◽  
Single Cells ◽  
Chromosomal Translocation ◽  
Pcr Amplification ◽  
Positive Control ◽  
Total Dna

Using the polymerase chain reaction (PCR) technique and total DNA extracts of Hodgkin's disease (HD)-involved lymph nodes, the t(14;18)(q32;q21) translocation was detected in 37 of 115 (32.2%) cases studied. No correlation was found between the presence of this translocation and bcl-2 protein expression in Hodgkin and Reed-Sternberg (HRS) cells detected by immunohistochemistry in 58 of 96 (60.4%) cases. To identify the cells carrying the t(14;18) translocation, single-cell DNA from HRS cells isolated by micromanipulation from frozen tissue sections of lymph nodes was investigated by PCR amplification. Eleven cases showing a positive band of the same size in at least two of five PCR experiments performed on the same total DNA extract were selected for single-cell PCR. We postulated that this repeated successful amplification could be indicative of the presence of the t(14;18) translocation in the neoplastic HRS cells. Single cells from frozen tumor sections of the t(14;18)-positive OCI LY8 cell line grafted into nude mice served as a positive control. The bcl-2/JH rearrangement, involved in this translocation, could be amplified from single-cell DNA of the latter tumor, whereas, in all of the HD cases, HRS cells were found to be negative. We conclude that the t(14;18) translocation is not localized in HRS cells, but in nonmalignant B bystander lymphocytes, admixed with these neoplastic cells.

Sign in / Sign up

Export Citation Format

Share Document