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

Paola Parrella, Maria Luana Poeta, Antonietta Pia Gallo, Maria Prencipe, Marina Scintu, Adolfo Apicella, Raffaele Rossiello, Giuseppina Liguoro, Davide Seripa, Carolina Gravina, Carla Rabitti, Monica Rinaldi, Theresa Nicol, Stefania Tommasi, Angelo Paradiso, Francesco Schittulli, Vittorio Altomare, Vito Michele Fazio

Research output: Contribution to journalArticle

Abstract

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, TRβ1, RARβ2, 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 CDHI gene (P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of the ESR1 promoter, and methylation at CDH1, TRβ1, GSTP1, and CCND2 loci (P <0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RARβ2 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.

Original languageEnglish
Pages (from-to)5349-5354
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number16
DOIs
Publication statusPublished - Aug 15 2004

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Neoplasm Genes
Methylation
Breast Neoplasms
Genes
CpG Islands
Breast
Research Design
Neoplasm Metastasis
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors. / Parrella, Paola; Poeta, Maria Luana; Gallo, Antonietta Pia; Prencipe, Maria; Scintu, Marina; Apicella, Adolfo; Rossiello, Raffaele; Liguoro, Giuseppina; Seripa, Davide; Gravina, Carolina; Rabitti, Carla; Rinaldi, Monica; Nicol, Theresa; Tommasi, Stefania; Paradiso, Angelo; Schittulli, Francesco; Altomare, Vittorio; Fazio, Vito Michele.

In: Clinical Cancer Research, Vol. 10, No. 16, 15.08.2004, p. 5349-5354.

Research output: Contribution to journalArticle

Parrella, P, Poeta, ML, Gallo, AP, Prencipe, M, Scintu, M, Apicella, A, Rossiello, R, Liguoro, G, Seripa, D, Gravina, C, Rabitti, C, Rinaldi, M, Nicol, T, Tommasi, S, Paradiso, A, Schittulli, F, Altomare, V & Fazio, VM 2004, 'Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors', Clinical Cancer Research, vol. 10, no. 16, pp. 5349-5354. https://doi.org/10.1158/1078-0432.CCR-04-0555
Parrella, Paola ; Poeta, Maria Luana ; Gallo, Antonietta Pia ; Prencipe, Maria ; Scintu, Marina ; Apicella, Adolfo ; Rossiello, Raffaele ; Liguoro, Giuseppina ; Seripa, Davide ; Gravina, Carolina ; Rabitti, Carla ; Rinaldi, Monica ; Nicol, Theresa ; Tommasi, Stefania ; Paradiso, Angelo ; Schittulli, Francesco ; Altomare, Vittorio ; Fazio, Vito Michele. / Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 16. pp. 5349-5354.
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abstract = "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, TRβ1, RARβ2, 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 CDHI gene (P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of the ESR1 promoter, and methylation at CDH1, TRβ1, GSTP1, and CCND2 loci (P <0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RARβ2 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.",
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T1 - Nonrandom distribution of aberrant promoter methylation of cancer-related genes in sporadic breast tumors

AU - Parrella, Paola

AU - Poeta, Maria Luana

AU - Gallo, Antonietta Pia

AU - Prencipe, Maria

AU - Scintu, Marina

AU - Apicella, Adolfo

AU - Rossiello, Raffaele

AU - Liguoro, Giuseppina

AU - Seripa, Davide

AU - Gravina, Carolina

AU - Rabitti, Carla

AU - Rinaldi, Monica

AU - Nicol, Theresa

AU - Tommasi, Stefania

AU - Paradiso, Angelo

AU - Schittulli, Francesco

AU - Altomare, Vittorio

AU - Fazio, Vito Michele

PY - 2004/8/15

Y1 - 2004/8/15

N2 - 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, TRβ1, RARβ2, 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 CDHI gene (P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of the ESR1 promoter, and methylation at CDH1, TRβ1, GSTP1, and CCND2 loci (P <0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RARβ2 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.

AB - 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, TRβ1, RARβ2, 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 CDHI gene (P = 0.02). The analysis of methylation distribution indicates a statistically significant association between methylation of the ESR1 promoter, and methylation at CDH1, TRβ1, GSTP1, and CCND2 loci (P <0.03). Methylated status of the BRCA1 promoter was inversely correlated with methylation at the RARβ2 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.

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