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...
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| Veröffentlicht in: | Clinical cancer research 2004-08, Vol.10 (16), p.5349-5354 |
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| creator | PARRELLA, Paola LUANA POETA, Maria RABITTI, Carla RINALDI, Monica NICOL, Theresa TOMMASI, Stefania PARADISO, Angelo SCHITTULLI, Francesco ALTOMARE, Vittorio FAZIO, Vito Michele GALLO, Antonietta Pia PRENCIPE, Maria SCINTU, Marina APICELLA, Adolfo ROSSIELLO, Raffaele LIGUORO, Giuseppina SERIPA, Davide GRAVINA, Carolina |
| description | 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. |
| doi_str_mv | 10.1158/1078-0432.CCR-04-0555 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66815824</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17686370</sourcerecordid><originalsourceid>FETCH-LOGICAL-c546t-bf27e01d102dd953c35917c0342c166e0c2b45c2b0288bbe7f8f63e6ea444b563</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhiMEoqXwE0C-gOCQ4vH3HkuAglQ-VMrZcpwJa5TEWzsR6r_H6W7VG1zsV_Yz45GfqnoO9BRAmrdAtamp4Oy0aS5LqKmU8kF1DFLqmjMlH5Z8xxxVT3L-TSkIoOJxdQSSMwMajqvwNU7JTV0cyfuQ5xTaZQ5xIrEnZy2mcjWT7ymOccZEvuC8vRncHdC4yWOqL7EcYUfOccJMwkR-7GJyXfDkXUKXZ3K1jDHlp9Wj3g0Znx32k-rnxw9Xzaf64tv55-bsovZSqLlue6aRQgeUdd1Gcs_lBrSnXDAPSiH1rBWyLJQZ07aoe9MrjgqdEKKVip9Ur_Z9dyleL5hnO4bscRjchHHJVilT_o-JAr7-JwhGSyOU2sB_e4JWRnFNCyj3oE8x54S93aUwunRjgdrVm12d2NWJLd5KsKu3Uvfi8MDSjtjdVx1EFeDlAXDZu6EvYnzI95yiUgu6DvBmz23Dr-2fkND6W0sJM7rkt7dzKCu52PC_FSSuZA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17686370</pqid></control><display><type>article</type><title>Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>PARRELLA, Paola ; LUANA POETA, Maria ; RABITTI, Carla ; RINALDI, Monica ; NICOL, Theresa ; TOMMASI, Stefania ; PARADISO, Angelo ; SCHITTULLI, Francesco ; ALTOMARE, Vittorio ; FAZIO, Vito Michele ; GALLO, Antonietta Pia ; PRENCIPE, Maria ; SCINTU, Marina ; APICELLA, Adolfo ; ROSSIELLO, Raffaele ; LIGUORO, Giuseppina ; SERIPA, Davide ; GRAVINA, Carolina</creator><creatorcontrib>PARRELLA, Paola ; LUANA POETA, Maria ; RABITTI, Carla ; RINALDI, Monica ; NICOL, Theresa ; TOMMASI, Stefania ; PARADISO, Angelo ; SCHITTULLI, Francesco ; ALTOMARE, Vittorio ; FAZIO, Vito Michele ; GALLO, Antonietta Pia ; PRENCIPE, Maria ; SCINTU, Marina ; APICELLA, Adolfo ; ROSSIELLO, Raffaele ; LIGUORO, Giuseppina ; SERIPA, Davide ; GRAVINA, Carolina</creatorcontrib><description>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.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-0555</identifier><identifier>PMID: 15328171</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Analysis of Variance ; Antineoplastic agents ; Biological and medical sciences ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Dinucleoside Phosphates - genetics ; DNA Methylation ; DNA, Neoplasm - genetics ; DNA, Neoplasm - isolation & purification ; Female ; Genes, Tumor Suppressor ; Humans ; Medical sciences ; Pharmacology. Drug treatments ; Polymerase Chain Reaction ; Promoter Regions, Genetic - genetics ; Tumors</subject><ispartof>Clinical cancer research, 2004-08, Vol.10 (16), p.5349-5354</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-bf27e01d102dd953c35917c0342c166e0c2b45c2b0288bbe7f8f63e6ea444b563</citedby><cites>FETCH-LOGICAL-c546t-bf27e01d102dd953c35917c0342c166e0c2b45c2b0288bbe7f8f63e6ea444b563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3356,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16057400$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15328171$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PARRELLA, Paola</creatorcontrib><creatorcontrib>LUANA POETA, Maria</creatorcontrib><creatorcontrib>RABITTI, Carla</creatorcontrib><creatorcontrib>RINALDI, Monica</creatorcontrib><creatorcontrib>NICOL, Theresa</creatorcontrib><creatorcontrib>TOMMASI, Stefania</creatorcontrib><creatorcontrib>PARADISO, Angelo</creatorcontrib><creatorcontrib>SCHITTULLI, Francesco</creatorcontrib><creatorcontrib>ALTOMARE, Vittorio</creatorcontrib><creatorcontrib>FAZIO, Vito Michele</creatorcontrib><creatorcontrib>GALLO, Antonietta Pia</creatorcontrib><creatorcontrib>PRENCIPE, Maria</creatorcontrib><creatorcontrib>SCINTU, Marina</creatorcontrib><creatorcontrib>APICELLA, Adolfo</creatorcontrib><creatorcontrib>ROSSIELLO, Raffaele</creatorcontrib><creatorcontrib>LIGUORO, Giuseppina</creatorcontrib><creatorcontrib>SERIPA, Davide</creatorcontrib><creatorcontrib>GRAVINA, Carolina</creatorcontrib><title>Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>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.</description><subject>Analysis of Variance</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Dinucleoside Phosphates - genetics</subject><subject>DNA Methylation</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - isolation & purification</subject><subject>Female</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymerase Chain Reaction</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Tumors</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhiMEoqXwE0C-gOCQ4vH3HkuAglQ-VMrZcpwJa5TEWzsR6r_H6W7VG1zsV_Yz45GfqnoO9BRAmrdAtamp4Oy0aS5LqKmU8kF1DFLqmjMlH5Z8xxxVT3L-TSkIoOJxdQSSMwMajqvwNU7JTV0cyfuQ5xTaZQ5xIrEnZy2mcjWT7ymOccZEvuC8vRncHdC4yWOqL7EcYUfOccJMwkR-7GJyXfDkXUKXZ3K1jDHlp9Wj3g0Znx32k-rnxw9Xzaf64tv55-bsovZSqLlue6aRQgeUdd1Gcs_lBrSnXDAPSiH1rBWyLJQZ07aoe9MrjgqdEKKVip9Ur_Z9dyleL5hnO4bscRjchHHJVilT_o-JAr7-JwhGSyOU2sB_e4JWRnFNCyj3oE8x54S93aUwunRjgdrVm12d2NWJLd5KsKu3Uvfi8MDSjtjdVx1EFeDlAXDZu6EvYnzI95yiUgu6DvBmz23Dr-2fkND6W0sJM7rkt7dzKCu52PC_FSSuZA</recordid><startdate>20040815</startdate><enddate>20040815</enddate><creator>PARRELLA, Paola</creator><creator>LUANA POETA, Maria</creator><creator>RABITTI, Carla</creator><creator>RINALDI, Monica</creator><creator>NICOL, Theresa</creator><creator>TOMMASI, Stefania</creator><creator>PARADISO, Angelo</creator><creator>SCHITTULLI, Francesco</creator><creator>ALTOMARE, Vittorio</creator><creator>FAZIO, Vito Michele</creator><creator>GALLO, Antonietta Pia</creator><creator>PRENCIPE, Maria</creator><creator>SCINTU, Marina</creator><creator>APICELLA, Adolfo</creator><creator>ROSSIELLO, Raffaele</creator><creator>LIGUORO, Giuseppina</creator><creator>SERIPA, Davide</creator><creator>GRAVINA, Carolina</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040815</creationdate><title>Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors</title><author>PARRELLA, Paola ; LUANA POETA, Maria ; RABITTI, Carla ; RINALDI, Monica ; NICOL, Theresa ; TOMMASI, Stefania ; PARADISO, Angelo ; SCHITTULLI, Francesco ; ALTOMARE, Vittorio ; FAZIO, Vito Michele ; GALLO, Antonietta Pia ; PRENCIPE, Maria ; SCINTU, Marina ; APICELLA, Adolfo ; ROSSIELLO, Raffaele ; LIGUORO, Giuseppina ; SERIPA, Davide ; GRAVINA, Carolina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-bf27e01d102dd953c35917c0342c166e0c2b45c2b0288bbe7f8f63e6ea444b563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Analysis of Variance</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Dinucleoside Phosphates - genetics</topic><topic>DNA Methylation</topic><topic>DNA, Neoplasm - genetics</topic><topic>DNA, Neoplasm - isolation & purification</topic><topic>Female</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymerase Chain Reaction</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PARRELLA, Paola</creatorcontrib><creatorcontrib>LUANA POETA, Maria</creatorcontrib><creatorcontrib>RABITTI, Carla</creatorcontrib><creatorcontrib>RINALDI, Monica</creatorcontrib><creatorcontrib>NICOL, Theresa</creatorcontrib><creatorcontrib>TOMMASI, Stefania</creatorcontrib><creatorcontrib>PARADISO, Angelo</creatorcontrib><creatorcontrib>SCHITTULLI, Francesco</creatorcontrib><creatorcontrib>ALTOMARE, Vittorio</creatorcontrib><creatorcontrib>FAZIO, Vito Michele</creatorcontrib><creatorcontrib>GALLO, Antonietta Pia</creatorcontrib><creatorcontrib>PRENCIPE, Maria</creatorcontrib><creatorcontrib>SCINTU, Marina</creatorcontrib><creatorcontrib>APICELLA, Adolfo</creatorcontrib><creatorcontrib>ROSSIELLO, Raffaele</creatorcontrib><creatorcontrib>LIGUORO, Giuseppina</creatorcontrib><creatorcontrib>SERIPA, Davide</creatorcontrib><creatorcontrib>GRAVINA, Carolina</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PARRELLA, Paola</au><au>LUANA POETA, Maria</au><au>RABITTI, Carla</au><au>RINALDI, Monica</au><au>NICOL, Theresa</au><au>TOMMASI, Stefania</au><au>PARADISO, Angelo</au><au>SCHITTULLI, Francesco</au><au>ALTOMARE, Vittorio</au><au>FAZIO, Vito Michele</au><au>GALLO, Antonietta Pia</au><au>PRENCIPE, Maria</au><au>SCINTU, Marina</au><au>APICELLA, Adolfo</au><au>ROSSIELLO, Raffaele</au><au>LIGUORO, Giuseppina</au><au>SERIPA, Davide</au><au>GRAVINA, Carolina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2004-08-15</date><risdate>2004</risdate><volume>10</volume><issue>16</issue><spage>5349</spage><epage>5354</epage><pages>5349-5354</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><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 , 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.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>15328171</pmid><doi>10.1158/1078-0432.CCR-04-0555</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical cancer research, 2004-08, Vol.10 (16), p.5349-5354 |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Analysis of Variance Antineoplastic agents Biological and medical sciences Breast Neoplasms - genetics Breast Neoplasms - pathology Dinucleoside Phosphates - genetics DNA Methylation DNA, Neoplasm - genetics DNA, Neoplasm - isolation & purification Female Genes, Tumor Suppressor Humans Medical sciences Pharmacology. Drug treatments Polymerase Chain Reaction Promoter Regions, Genetic - genetics Tumors |
| title | Nonrandom Distribution of Aberrant Promoter Methylation of Cancer-Related Genes in Sporadic Breast Tumors |
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