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Title: Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis

Abstract

Non-Hodgkin lymphoma is a common feature of AIDS. Approximately 30-40% of these tumors exhibit clinical features suggestive of endemic Burkitt lymphoma: they are aggressive malignancies that occur in association with Epstein-Barr virus infection, they arise in the setting of immunosuppression, and they carry t(8;14) translocations without detectable rearrangement of the MYC oncogene. To understand the molecular basis of these parallels, the authors analyzed a case of Epstein-Barr-positive AIDS-associated undifferentiated lymphoma. Southern blots show that the tumor exhibits immunoglobulin joining segment rearrangement but no rearrangement of the MYC oncogene. Cloning of the rearranged joining segment allowed the isolation of recombinant clones encompassing the translocation breakpoint, and sequencing of the translocation junction disclosed that the breakpoint is situated 7 base pairs from the chromosome 14 site involved in a previously described endemic Burkitt lymphoma translocation. Furthermore, the breakpoint is situated far from MYC on chromosome 8, a constant finding in endemic Burkitt lymphomas. That the molecular architecture of the translocation in this case is strikingly similar to previously analyzed translocations from endemic Burkitt lymphomas strongly suggests that common molecular mechanisms must be operative in the pathogenesis of these tumors.

Authors:
; ;  [1];  [2];  [3]
  1. (Fels Institute for Cancer Research and Molecular Biology, Philadelphia, PA (USA))
  2. (Univ. of Pennsylvania School of Medicine, Philadelphia (USA))
  3. (Memorial Sloan Kettering Institute, New York, NY (USA))
Publication Date:
OSTI Identifier:
6906459
Alternate Identifier(s):
OSTI ID: 6906459
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA); Journal Volume: 86:22
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; AIDS; PATHOGENESIS; CHROMOSOMAL ABERRATIONS; DNA SEQUENCING; LYMPHOMAS; GENETICS; ENZYME IMMUNOASSAY; HETEROCHROMOSOMES; IMMUNOGLOBULINS; MEN; ONCOGENES; PATIENTS; PHOSPHORUS 32; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOASSAY; BIOLOGY; CHROMOSOMES; DAYS LIVING RADIOISOTOPES; DISEASES; GENES; GLOBULINS; HEMIC DISEASES; IMMUNE SYSTEM DISEASES; IMMUNOASSAY; INFECTIOUS DISEASES; ISOTOPES; LIGHT NUCLEI; MALES; MAMMALS; MAN; MUTATIONS; NEOPLASMS; NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; PHOSPHORUS ISOTOPES; PRIMATES; PROTEINS; RADIOISOTOPES; STRUCTURAL CHEMICAL ANALYSIS; VERTEBRATES; VIRAL DISEASES 550401* -- Genetics-- Tracer Techniques

Citation Formats

Haluska, F.G., Russo, G., Croce, C.M., Kant, J., and Andreef, M.. Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis. United States: N. p., 1989. Web. doi:10.1073/pnas.86.22.8907.
Haluska, F.G., Russo, G., Croce, C.M., Kant, J., & Andreef, M.. Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis. United States. doi:10.1073/pnas.86.22.8907.
Haluska, F.G., Russo, G., Croce, C.M., Kant, J., and Andreef, M.. Wed . "Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis". United States. doi:10.1073/pnas.86.22.8907.
@article{osti_6906459,
title = {Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis},
author = {Haluska, F.G. and Russo, G. and Croce, C.M. and Kant, J. and Andreef, M.},
abstractNote = {Non-Hodgkin lymphoma is a common feature of AIDS. Approximately 30-40% of these tumors exhibit clinical features suggestive of endemic Burkitt lymphoma: they are aggressive malignancies that occur in association with Epstein-Barr virus infection, they arise in the setting of immunosuppression, and they carry t(8;14) translocations without detectable rearrangement of the MYC oncogene. To understand the molecular basis of these parallels, the authors analyzed a case of Epstein-Barr-positive AIDS-associated undifferentiated lymphoma. Southern blots show that the tumor exhibits immunoglobulin joining segment rearrangement but no rearrangement of the MYC oncogene. Cloning of the rearranged joining segment allowed the isolation of recombinant clones encompassing the translocation breakpoint, and sequencing of the translocation junction disclosed that the breakpoint is situated 7 base pairs from the chromosome 14 site involved in a previously described endemic Burkitt lymphoma translocation. Furthermore, the breakpoint is situated far from MYC on chromosome 8, a constant finding in endemic Burkitt lymphomas. That the molecular architecture of the translocation in this case is strikingly similar to previously analyzed translocations from endemic Burkitt lymphomas strongly suggests that common molecular mechanisms must be operative in the pathogenesis of these tumors.},
doi = {10.1073/pnas.86.22.8907},
journal = {Proceedings of the National Academy of Sciences of the United States of America; (USA)},
number = ,
volume = 86:22,
place = {United States},
year = {Wed Nov 01 00:00:00 EST 1989},
month = {Wed Nov 01 00:00:00 EST 1989}
}
  • The electrokinetic behavior of Burkitt lymphoma P 3H-R1 cells were studied following x irradiation. The surface charge of irradiated cells decreased progressively with time after x-ray treatment, as compared with a mean mobility value (-0.677 +- 0.045 $mu$sec$sup -1$ V$sup -1$ cm) of non-irradiated cells. The frequency distribution of cells treated with 3,000 R 4 h previously showed quite a different peak of lower mobility than that of non-irradiated cells with the boundary of -0.550 $mu$sec$sup -1$ V$sup -1$ cm. Percentages of cells which showed the higher mobility than the boundary value 4 h after irradiation with 30, 50, 65,more » 100, 200, or 3,000 R were in accord with the percentage of cells which showed colony-forming ability in soft agar, respectively. Following cell proliferation the population of electrokinetically intact cells increased with time after irradiation; these values also coincided with the population of colony- forming cells, Thus, the present results indicate that there is a close relation between loss of negative surface charge and loss of colony forming ability in irradiated cells, suggesting that loss of colony forming ability of the cells may be determined as early as 4 h after irradiation. (auth)« less
  • Chromosomal translocations in Burkitt lymphoma and mouse plasmacytomas typically lie within or near the protooncogene MYC. In some instances, however, these tumors contain variant translocations with breakpoints located more distant from and downstream of MYC, in a domain commonly known as pvt-1. Until now, there has been no evidence that pvt-1 marks the location of a functional gene. Here the authors report the identification of a large transcriptional unit in human DNA that includes pvt-1. The authors have designated this unit as PVT. PVT begins 57 kilobase pairs downstream of MYC and occupies a minimum of 200 kilobase pairs ofmore » DNA. Some of the translocations that occur downstream of MYC in Burkitt lymphoma transect PVT; others lie between the two genes. None of the translocations they have studied appear to enhance transcription from an intact allele of PVT (indeed, they may inactivate that transcription), but some are associated with the production of abundant and anomalous 0.8- to 1.0-kilobase RNAs that contain the 5{prime} exon of PVT and sequences transcribed from the constant region of an immunoglobulin gene (the reciprocal participant in the translocation). Identification of PVT should facilitate the exploration of how translocations downstream of MYC and insertions of retroviral DNA in the vicinity of pvt-1 might contribute to tumorigenesis.« less