Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors
Purpose: In an effort to additionally determine the global patterns of CpG island hypermethylation in sporadic breast cancer, we searched for aberrant promoter methylation at 10 gene loci in 54 primary breast cancer and 10 breast benign lesions. Experimental Design: Genomic DNA sodium bisulfate conv...
Saved in:
Published in | Clinical cancer research Vol. 10; no. 16; pp. 5349 - 5354 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
15.08.2004
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Purpose: In an effort to additionally determine the global patterns of CpG island hypermethylation in sporadic breast cancer, we searched
for aberrant promoter methylation at 10 gene loci in 54 primary breast cancer and 10 breast benign lesions.
Experimental Design: Genomic DNA sodium bisulfate converted from benign and malignant tissues was used as template in methyl-specific PCR for
BRCA1 , p16 , ESR1 , GSTP1 , TR β 1 , RAR β 2 , HIC1 , APC , CCND2 , and CDH1 genes.
Results: The majority of the breast cancer (85%) showed aberrant methylation in at least 1 of the loci tested with half of them displaying
3 or more methylated genes. The highest frequency of aberrant promoter methylation was found for HIC1 (48%) followed by ESR1 (46%), and CDH1 (39%). Similar methylation frequencies were detected for breast benign lesions with the exception of the CDH1 gene ( P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of
the ESR1 promoter, and methylation at CDH1 , TR β 1 , GSTP1 , and CCND2 loci ( P < 0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RAR β 2 locus ( P < 0.03).
Conclusions: Our results suggest a nonrandom distribution for promoter hypermethylation in sporadic breast cancer, with tumor subsets
characterized by aberrant methylation of specific cancer-related genes. These breast cancer subgroups may represent separate
biological entities with potential differences in sensitivity to therapy, occurrence of metastasis, and overall prognosis. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-04-0555 |