Methylation of CpG dinucleotides and/or CCWGG motifs at the promoter of TP53 correlates with decreased gene expression in a subset of acute lymphoblastic leukemia patients

被引：63

作者：

Agirre, X ^{[1
]}

Vizmanos, JL ^{[1
]}

Calasanz, MJ ^{[1
]}

García-Delgado, M ^{[1
]}

Larráyoz, MJ ^{[1
]}

Novo, FJ ^{[1
]}

机构：

[1] Univ Navarra, Sch Sci, Dept Genet, E-31080 Pamplona, Navarra, Spain

来源：

ONCOGENE | 2003年 / 22卷 / 07期

关键词：

TP53; methylation analysis; promoter analysis; gene expression; ALL;

D O I：

10.1038/sj.onc.1206236

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

It has been shown that methylation of CpG dinucleotides located in the promoter region of TP53 is associated with low expression levels of this gene. We have analysed the methylation status of one CpG dinucleotide and of three CCWGG motifs, also located in the promoter region of the gene, in bone marrow samples obtained from patients with acute lymphoblastic leukemia (ALL). Eight out of 25 samples analysed showed methylation of either the CpG dinucleotide, the CCWGG motifs or both. Relative to nonmethylated leukemia samples, TP53 expression levels were decreased in all methylated samples in which TP53 expression could be measured. Methylation of CpG and CCWGG motifs in the promoter of TP53 could represent a novel mechanism leading to functional impairment of this tumor suppressor gene in ALL.

引用

页码：1070 / 1072

页数：3

共 15 条

[1] Exon concatenation to increase the efficiency of mutation screening by DGGE [J].

Agirre, X ;

García-Delgado, M ;

Calasanz, MJ ;

Larráyoz, MJ ;

Novo, FJ ;

Vizmanos, JL .

BIOTECHNIQUES, 2002, 32 (05) :1064-+

[2] THE 5' REGION OF THE P53 GENE - EVOLUTIONARY CONSERVATION AND EVIDENCE FOR A NEGATIVE REGULATORY ELEMENT [J].

BIENZTADMOR, B ;

ZAKUTHOURI, R ;

LIBRESCO, S ;

GIVOL, D ;

OREN, M .

EMBO JOURNAL, 1985, 4 (12) :3209-3213

[3] Dietary selenium and arsenic affect DNA methylation in vitro in Caco-2 cells and in vivo in rat liver and colon [J].

Davis, CD ;

Uthus, EO ;

Finley, JW .

JOURNAL OF NUTRITION, 2000, 130 (12) :2903-2909

[4]

Herman JG, 1996, CANCER RES, V56, P722

[5] Methylation in the p53 promoter is a supplementary route to breast carcinogenesis: Correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma [J].

Kang, JH ;

Kim, SJ ;

Noh, DY ;

Park, IA ;

Choe, KJ ;

Yoo, OJ ;

Kang, HS .

LABORATORY INVESTIGATION, 2001, 81 (04) :573-579

[6] C(m)C(A/T)GG DNA methylation in mature B cell lymphoma gene silencing [J].

Malone, CS ;

Miner, MD ;

Doerr, JR ;

Jackson, JP ;

Jacobsen, SE ;

Wall, R ;

Teitell, M .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10404-10409

[7] Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: A model for a mechanism of carcinogenesis [J].

Mass, MJ ;

Wang, LJ .

MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH, 1997, 386 (03) :263-277

[8]

Pogribny IP, 2000, CANCER RES, V60, P588

[9] Reduction of p53 gene expression in human primary hepatocellular carcinoma is associated with promoter region methylation without coding region mutation [J].

Pogribny, IP ;

James, SJ .

CANCER LETTERS, 2002, 176 (02) :169-174

[10] The clinical significance of mutations of the P53 tumour suppressor gene in haematological malignancies [J].

Preudhomme, C ;

Fenaux, P .

BRITISH JOURNAL OF HAEMATOLOGY, 1997, 98 (03) :502-511

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