Purpose: In an effort to additionally determine theglobal patterns of CpG island hypermethylation in sporadicbreast cancer, we searched for aberrant promoter methylationat 10 gene loci in 54 primary breast cancer and 10breast benign lesions.Experimental Design: Genomic DNA sodium bisulfateconverted from benign and malignant tissues was used astemplate in methyl-specific PCR for BRCA1, p16, ESR1,GSTP1, TR1, RAR2, HIC1, APC, CCND2, and CDH1genes.Results: The majority of the breast cancer (85%)showed aberrant methylation in at least 1 of the loci testedwith half of them displaying 3 or more methylated genes.The highest frequency of aberrant promoter methylationwas found for HIC1 (48%) followed by ESR1 (46%), andCDH1 (39%). Similar methylation frequencies were detectedfor breast benign lesions with the exception of the CDH1gene (P 0.02). The analysis of methylation distributionindicates a statistically significant association between methylationof the ESR1 promoter, and methylation at CDH1,TR1, GSTP1, and CCND2 loci (P < 0.03). Methylatedstatus of the BRCA1 promoter was inversely correlated withmethylation at the RAR2 locus (P < 0.03).Conclusions: Our results suggest a nonrandom distributionfor promoter hypermethylation in sporadic breastcancer, with tumor subsets characterized by aberrant methylationof specific cancer-related genes. These breast cancersubgroups may represent separate biological entities withpotential differences in sensitivity to therapy, occurrence ofmetastasis, and overall prognosis.

Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors

Rabitti C;Altomare V;Fazio VM
2004-01-01

Abstract

Purpose: In an effort to additionally determine theglobal patterns of CpG island hypermethylation in sporadicbreast cancer, we searched for aberrant promoter methylationat 10 gene loci in 54 primary breast cancer and 10breast benign lesions.Experimental Design: Genomic DNA sodium bisulfateconverted from benign and malignant tissues was used astemplate in methyl-specific PCR for BRCA1, p16, ESR1,GSTP1, TR1, RAR2, HIC1, APC, CCND2, and CDH1genes.Results: The majority of the breast cancer (85%)showed aberrant methylation in at least 1 of the loci testedwith half of them displaying 3 or more methylated genes.The highest frequency of aberrant promoter methylationwas found for HIC1 (48%) followed by ESR1 (46%), andCDH1 (39%). Similar methylation frequencies were detectedfor breast benign lesions with the exception of the CDH1gene (P 0.02). The analysis of methylation distributionindicates a statistically significant association between methylationof the ESR1 promoter, and methylation at CDH1,TR1, GSTP1, and CCND2 loci (P < 0.03). Methylatedstatus of the BRCA1 promoter was inversely correlated withmethylation at the RAR2 locus (P < 0.03).Conclusions: Our results suggest a nonrandom distributionfor promoter hypermethylation in sporadic breastcancer, with tumor subsets characterized by aberrant methylationof specific cancer-related genes. These breast cancersubgroups may represent separate biological entities withpotential differences in sensitivity to therapy, occurrence ofmetastasis, and overall prognosis.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/7015
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