TY - JOUR
T1 - Impact of chromosomal rearrangement upon DNA methylation patterns in leukemia
AU - Byun, Hyang Min
AU - Eshaghian, Shahrooz
AU - Douer, Dan
AU - Trent, Jonathen
AU - Garcia-Manero, Guillermo
AU - Bhatia, Ravi
AU - Siegmund, Kim
AU - Yang, Allen S.
N1 - Publisher Copyright:
© 2017 Hyang-Min Byun et al.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST). In this study, the DNA methylation profile of CML was more closely related to APL, another myeloid leukemia, than Ph+ ALL. Although DNA methylation profiles were consistent within a specific tumor type, overall DNA methylation profiles were no influenced by BCR-ABL gene translocation in the cancers and tissues studied. We conclude that DNA methylation profiles may reflect the cell of origin in cancers rather than the chromosomal lesions involved in leukemogenesis.
AB - Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST). In this study, the DNA methylation profile of CML was more closely related to APL, another myeloid leukemia, than Ph+ ALL. Although DNA methylation profiles were consistent within a specific tumor type, overall DNA methylation profiles were no influenced by BCR-ABL gene translocation in the cancers and tissues studied. We conclude that DNA methylation profiles may reflect the cell of origin in cancers rather than the chromosomal lesions involved in leukemogenesis.
KW - 5-azacytidine
KW - Acute Lymphoblastic Leukemia
KW - Acute Promyelocytic Leukemia
KW - Chronic Myelogenous Leukemia
KW - DNA methylation
KW - Gastrointestinal Stromal Tumor
KW - Philadelphia Chromosome
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U2 - 10.1515/med-2017-0014
DO - 10.1515/med-2017-0014
M3 - Article
C2 - 28730166
AN - SCOPUS:85019073661
SN - 2391-5463
VL - 12
SP - 76
EP - 85
JO - Open Medicine (Poland)
JF - Open Medicine (Poland)
IS - 1
ER -