HIC1 hypermethylation is a late event in hematopoietic neoplasms.
HIC1, a candidate tumor suppressor gene on 17p13.3, is hypermethylated and silenced in a large number of solid tumors. To determine its potential role in leukemias, we studied its methylation status in normal and neoplastic hematopoietic cells. We found HIC1 to be unmethylated in peripheral blood cells, bone marrow cells, and CD34+ cells. HIC1 was rarely methylated in newly diagnosed acute myelogenous leukemias (10%) but was relatively frequently methylated in newly diagnosed non-Hodgkin's lymphoma (25%), acute lymphocytic leukemia (ALL; 53%), and chronic-phase chronic myelogenous leukemia (50%). By contrast, HIC1 was hypermethylated in 100% of recurrent ALL and 100% of blast crisis chronic myelogenous leukemia. In two patients with ALL for whom paired diagnosis/relapse samples were available, HIC1 was unmethylated at diagnosis but was highly methylated at relapse after a chemotherapy-induced complete remission. HIC1 methylation, therefore, seems to be a progression event in hematopoietic neoplasms.
Issa
J P
JP
The Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Zehnbauer
B A
BA
Kaufmann
S H
SH
Biel
M A
MA
Baylin
S B
SB
D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D015252:Deoxyribonucleases, Type II Site-Specific; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D007938:Leukemia / Q000235:genetics*; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; C096870:Hic1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D015252:Deoxyribonucleases, Type II Site-Specific; C038565:GCGGCCGC-specific type II deoxyribonucleases