Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation

Paul G. Corn, Steven J. Kuerbitz, Max M. Van Noesel, Manel Esteller, Nicole Compitello, Stephen B Baylin, James G. Herman

Research output: Contribution to journalArticle

Abstract

The p73 gene is located on 1p36.2-3, a region that is frequently deleted in human cancer. Because p73 encodes for a protein that is both structurally and functionally homologous to the p53 protein, p73 has been postulated to be a candidate tumor suppressor gene. To date, however, mutations of p73 have not been found. To study methylation of the p73 5'CpG island, a human bacterial artificial chromosome clone containing exon 1 and the 5' region of p73 was isolated. There was no evidence for p73 exon 1 methylation in normal tissue. In contrast, p73 was aberrantly methylated in approximately 30% of primary acute lymphoblastic leukemias (ALLs) and Burkitt's lymphomas. There was no evidence for methylation in any other types of hematological malignancies or solid tumors examined. In both leukemia cell lines and primary ALLs, methylation was associated with transcriptional loss of p73 by reverse transcription-PCR. We used single-strand conformational polymorphisms to screen for point mutations in a series of primary ALLs and found no mutations leading to a change in protein structure. Our results show that methylation of p73 is a frequent event in specific types of hematological malignancies and suggest that epigenetic silencing of p73 could have important consequences for cell-cycle regulation.

Original languageEnglish (US)
Pages (from-to)3352-3356
Number of pages5
JournalCancer Research
Volume59
Issue number14
StatePublished - Jul 15 1999

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CpG Islands
Burkitt Lymphoma
Gene Silencing
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methylation
Hematologic Neoplasms
Exons
Human Artificial Chromosomes
Bacterial Artificial Chromosomes
Mutation
Tumor Suppressor Genes
Point Mutation
Epigenomics
Reverse Transcription
Neoplasms
Cell Cycle
Leukemia
Proteins
Clone Cells
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Corn, P. G., Kuerbitz, S. J., Van Noesel, M. M., Esteller, M., Compitello, N., Baylin, S. B., & Herman, J. G. (1999). Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation. Cancer Research, 59(14), 3352-3356.

Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation. / Corn, Paul G.; Kuerbitz, Steven J.; Van Noesel, Max M.; Esteller, Manel; Compitello, Nicole; Baylin, Stephen B; Herman, James G.

In: Cancer Research, Vol. 59, No. 14, 15.07.1999, p. 3352-3356.

Research output: Contribution to journalArticle

Corn, PG, Kuerbitz, SJ, Van Noesel, MM, Esteller, M, Compitello, N, Baylin, SB & Herman, JG 1999, 'Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation', Cancer Research, vol. 59, no. 14, pp. 3352-3356.
Corn, Paul G. ; Kuerbitz, Steven J. ; Van Noesel, Max M. ; Esteller, Manel ; Compitello, Nicole ; Baylin, Stephen B ; Herman, James G. / Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation. In: Cancer Research. 1999 ; Vol. 59, No. 14. pp. 3352-3356.
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