Nature of frequent deletions in CEBPA.
C/EBPalpha (CCAAT/enhancer binding protein alpha) belongs to the family of leucine zipper transcription factors and is necessary for transcriptional control of granulocyte, adipocyte and hepatocyte differentiation, glucose metabolism and lung development. C/EBPalpha is encoded by an intronless gene. CEBPA mutations cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL) patients. In this study we identified in 41 individuals from 824 screened individuals (290 AML patients, 382 MDS patients, 56 NHL patients and 96 healthy individuals) a single class of 23 deletions in CEBPA gene which involved a direct repeat of at least 2 bp. These mutations are characterised by the loss of one of two same repeats at the ends of deleted sequence. Three most frequent repeats included in these deletions in CEBPA gene are CGCGAG (493-498_865-870), GCCAAGCAGC (508-517_907-916) and GG (486-487_885-886), all according to GenBank accession no. NM_004364.2. A mechanism for deletion formation between two repetitive sequences can be recombination events in the repair process. Double-stranded cut in DNA can initiate these recombination events of adjacent DNA sequences.
Fuchs
Ota
O
Institute of Hematology and Blood Transfusion, Department of Cell Physiology, U Nemocnice 1, 128 20 Prague 2, Czech Republic. Ota.Fuchs@uhkt.cz
Kostecka
Arnost
A
Provaznikova
Dana
D
Krasna
Blazena
B
Brezinova
Jana
J
Filkukova
Jitka
J
Kotlin
Roman
R
Kouba
Michal
M
Kobylka
Petr
P
Neuwirtova
Radana
R
Jonasova
Anna
A
Caniga
Miroslav
M
Schwarz
Jiri
J
Markova
Jana
J
Maaloufova
Jacqueline
J
Sponerova
Dana
D
Novakova
Ludmila
L
Cermak
Jaroslav
J
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human