TY - JOUR
T1 - Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation
AU - Corn, P G
AU - Kuerbitz, S J
AU - van Noesel, M M
AU - Esteller, M
AU - Compitello, N
AU - Baylin, S B
AU - Herman, J G
PY - 1999/7/15
Y1 - 1999/7/15
N2 - 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 tissues. 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.
AB - 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 tissues. 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.
KW - Adult
KW - Burkitt Lymphoma/genetics
KW - Child
KW - Chromosomes, Human, Pair 1/genetics
KW - CpG Islands
KW - DNA Methylation
KW - DNA Mutational Analysis
KW - DNA, Neoplasm/chemistry
KW - DNA-Binding Proteins/genetics
KW - Gene Expression Regulation, Neoplastic
KW - Genes, Tumor Suppressor
KW - Hematologic Neoplasms/genetics
KW - Humans
KW - Neoplasms/genetics
KW - Nuclear Proteins/genetics
KW - Polymorphism, Single-Stranded Conformational
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
KW - Promoter Regions, Genetic
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Transcription, Genetic
KW - Tumor Cells, Cultured
KW - Tumor Protein p73
KW - Tumor Suppressor Proteins
UR - https://pubmed.ncbi.nlm.nih.gov/10416592/
M3 - Article
C2 - 10416592
SN - 0008-5472
VL - 59
SP - 3352
EP - 3356
JO - Cancer research
JF - Cancer research
IS - 14
ER -