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CpG island methylation and expression of the secreted frizzled- related protein gene family in chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of mature neoplastic B cells indicating disruption of apoptosis. Restriction Landmark Genome Scanning was done to identify novel target genes silenced by CpG island methylation in CLL. Secreted frizzled-related prote...
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| Published in: | Cancer research (Chicago, Ill.) Ill.), 2006-01, Vol.66 (2), p.653-658 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | LIU, Te-Hui RAVAL, Aparna CHEN, Shih-Shih MATKOVIC, Jennifer J BYRD, John C PLASS, Christoph |
| description | B-cell chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of mature neoplastic B cells indicating disruption of apoptosis. Restriction Landmark Genome Scanning was done to identify novel target genes silenced by CpG island methylation in CLL. Secreted frizzled-related protein 4 (SFRP4), a negative regulator of the Wnt signaling pathway, was found to be frequently methylated in CLL samples. Wnt signaling has been shown to control normal apoptotic behavior and is required for normal B-cell development whereas aberrant activation of this pathway has been observed in CLL. We show aberrant DNA methylation and silencing of SFRP4, as well as of additional SFRP family members, in primary CLL samples. Induction of their expression in a dose-dependent manner following treatment with a demethylating agent, 5-aza-2'-deoxycytidine, was shown. Of the five SFRP family members studied in detail, SFRP1 was hypermethylated and down-regulated in all CLL patient samples studied, suggesting that this epigenetic event is a critical step during leukemogenesis. Our results suggest that silencing of SFRPs by CpG island methylation is one possible mechanism contributing to aberrant activation of Wnt signaling pathway in CLL. |
| doi_str_mv | 10.1158/0008-5472.can-05-3712 |
| format | article |
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Restriction Landmark Genome Scanning was done to identify novel target genes silenced by CpG island methylation in CLL. Secreted frizzled-related protein 4 (SFRP4), a negative regulator of the Wnt signaling pathway, was found to be frequently methylated in CLL samples. Wnt signaling has been shown to control normal apoptotic behavior and is required for normal B-cell development whereas aberrant activation of this pathway has been observed in CLL. We show aberrant DNA methylation and silencing of SFRP4, as well as of additional SFRP family members, in primary CLL samples. Induction of their expression in a dose-dependent manner following treatment with a demethylating agent, 5-aza-2'-deoxycytidine, was shown. Of the five SFRP family members studied in detail, SFRP1 was hypermethylated and down-regulated in all CLL patient samples studied, suggesting that this epigenetic event is a critical step during leukemogenesis. 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Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Membrane Proteins - biosynthesis ; Membrane Proteins - genetics ; Membrane Proteins - physiology ; Proto-Oncogene Proteins - biosynthesis ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - physiology ; Signal Transduction ; Wnt Proteins - physiology</subject><ispartof>Cancer research (Chicago, Ill.), 2006-01, Vol.66 (2), p.653-658</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c565t-ca12f0f5e7c3f062f62a253bac7772230364d3fe573e4023a62a6ff9191992353</citedby><cites>FETCH-LOGICAL-c565t-ca12f0f5e7c3f062f62a253bac7772230364d3fe573e4023a62a6ff9191992353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17650156$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16423993$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LIU, Te-Hui</creatorcontrib><creatorcontrib>RAVAL, Aparna</creatorcontrib><creatorcontrib>CHEN, Shih-Shih</creatorcontrib><creatorcontrib>MATKOVIC, Jennifer J</creatorcontrib><creatorcontrib>BYRD, John C</creatorcontrib><creatorcontrib>PLASS, Christoph</creatorcontrib><title>CpG island methylation and expression of the secreted frizzled- related protein gene family in chronic lymphocytic leukemia</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>B-cell chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of mature neoplastic B cells indicating disruption of apoptosis. Restriction Landmark Genome Scanning was done to identify novel target genes silenced by CpG island methylation in CLL. Secreted frizzled-related protein 4 (SFRP4), a negative regulator of the Wnt signaling pathway, was found to be frequently methylated in CLL samples. Wnt signaling has been shown to control normal apoptotic behavior and is required for normal B-cell development whereas aberrant activation of this pathway has been observed in CLL. We show aberrant DNA methylation and silencing of SFRP4, as well as of additional SFRP family members, in primary CLL samples. Induction of their expression in a dose-dependent manner following treatment with a demethylating agent, 5-aza-2'-deoxycytidine, was shown. Of the five SFRP family members studied in detail, SFRP1 was hypermethylated and down-regulated in all CLL patient samples studied, suggesting that this epigenetic event is a critical step during leukemogenesis. Our results suggest that silencing of SFRPs by CpG island methylation is one possible mechanism contributing to aberrant activation of Wnt signaling pathway in CLL.</description><subject>Azacitidine - analogs & derivatives</subject><subject>Azacitidine - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Transformation, Neoplastic</subject><subject>CpG Islands</subject><subject>DNA Methylation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Gene Expression Profiling</subject><subject>Gene Silencing</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - biosynthesis</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Intercellular Signaling Peptides and Proteins - physiology</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - physiopathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Membrane Proteins - biosynthesis</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - physiology</subject><subject>Proto-Oncogene Proteins - biosynthesis</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>Signal Transduction</subject><subject>Wnt Proteins - physiology</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqFkUtPGzEUhS1UBCHwE1p50-4m-DHXziyjiEIl1G5gbRnPNXE7r9oTiYE_j0dEzbLywj72d67tewj5zNmKc1hfM8bWBZRarJztCgaF1FyckAUHuS50WcInsvjHnJOLlH5nCZzBGTnnqhSyquSCvG2HWxpSY7uatjjupsaOoe_orPFliJjSLHtPxx3ShC7iiDX1Mby-NlgXNGJ25J0h9iOGjj5jh9TbNjQTzdLtYt8FR5upHXa9m8Z5jfs_2AZ7SU69bRJeHeYlefx-87C9K-5_3f7Ybu4LBwrGwlkuPPOA2knPlPBKWAHyyTqttRCSSVXW0iNoiSUT0uZz5X3F86iEBLkk3z7q5jf-3WMaTRuSwyZ_Gvt9MpqptWJa_hfM9YBJUWUQPkAX-5QiejPE0No4Gc7MHI-ZW2_m1pvt5qdhYOZ4su_L4YL9U4v10XXIIwNfD4BNzjY-2s6FdOS0AsZByXeZAZnE</recordid><startdate>20060115</startdate><enddate>20060115</enddate><creator>LIU, Te-Hui</creator><creator>RAVAL, Aparna</creator><creator>CHEN, Shih-Shih</creator><creator>MATKOVIC, Jennifer J</creator><creator>BYRD, John C</creator><creator>PLASS, Christoph</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>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20060115</creationdate><title>CpG island methylation and expression of the secreted frizzled- related protein gene family in chronic lymphocytic leukemia</title><author>LIU, Te-Hui ; RAVAL, Aparna ; CHEN, Shih-Shih ; MATKOVIC, Jennifer J ; BYRD, John C ; PLASS, Christoph</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c565t-ca12f0f5e7c3f062f62a253bac7772230364d3fe573e4023a62a6ff9191992353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Azacitidine - analogs & derivatives</topic><topic>Azacitidine - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Transformation, Neoplastic</topic><topic>CpG Islands</topic><topic>DNA Methylation</topic><topic>Dose-Response Relationship, Drug</topic><topic>Gene Expression Profiling</topic><topic>Gene Silencing</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Intercellular Signaling Peptides and Proteins - biosynthesis</topic><topic>Intercellular Signaling Peptides and Proteins - genetics</topic><topic>Intercellular Signaling Peptides and Proteins - physiology</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - physiopathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><topic>Membrane Proteins - biosynthesis</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - physiology</topic><topic>Proto-Oncogene Proteins - biosynthesis</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - physiology</topic><topic>Signal Transduction</topic><topic>Wnt Proteins - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LIU, Te-Hui</creatorcontrib><creatorcontrib>RAVAL, Aparna</creatorcontrib><creatorcontrib>CHEN, Shih-Shih</creatorcontrib><creatorcontrib>MATKOVIC, Jennifer J</creatorcontrib><creatorcontrib>BYRD, John C</creatorcontrib><creatorcontrib>PLASS, Christoph</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>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LIU, Te-Hui</au><au>RAVAL, Aparna</au><au>CHEN, Shih-Shih</au><au>MATKOVIC, Jennifer J</au><au>BYRD, John C</au><au>PLASS, Christoph</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CpG island methylation and expression of the secreted frizzled- related protein gene family in chronic lymphocytic leukemia</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2006-01-15</date><risdate>2006</risdate><volume>66</volume><issue>2</issue><spage>653</spage><epage>658</epage><pages>653-658</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>B-cell chronic lymphocytic leukemia (CLL) is characterized by a clonal accumulation of mature neoplastic B cells indicating disruption of apoptosis. Restriction Landmark Genome Scanning was done to identify novel target genes silenced by CpG island methylation in CLL. Secreted frizzled-related protein 4 (SFRP4), a negative regulator of the Wnt signaling pathway, was found to be frequently methylated in CLL samples. Wnt signaling has been shown to control normal apoptotic behavior and is required for normal B-cell development whereas aberrant activation of this pathway has been observed in CLL. We show aberrant DNA methylation and silencing of SFRP4, as well as of additional SFRP family members, in primary CLL samples. Induction of their expression in a dose-dependent manner following treatment with a demethylating agent, 5-aza-2'-deoxycytidine, was shown. Of the five SFRP family members studied in detail, SFRP1 was hypermethylated and down-regulated in all CLL patient samples studied, suggesting that this epigenetic event is a critical step during leukemogenesis. Our results suggest that silencing of SFRPs by CpG island methylation is one possible mechanism contributing to aberrant activation of Wnt signaling pathway in CLL.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>16423993</pmid><doi>10.1158/0008-5472.can-05-3712</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 2006-01, Vol.66 (2), p.653-658 |
| issn | 0008-5472 1538-7445 |
| language | eng |
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| subjects | Azacitidine - analogs & derivatives Azacitidine - pharmacology Biological and medical sciences Cell Transformation, Neoplastic CpG Islands DNA Methylation Dose-Response Relationship, Drug Gene Expression Profiling Gene Silencing Hematologic and hematopoietic diseases Humans Intercellular Signaling Peptides and Proteins - biosynthesis Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - physiology Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - physiopathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Membrane Proteins - biosynthesis Membrane Proteins - genetics Membrane Proteins - physiology Proto-Oncogene Proteins - biosynthesis Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - physiology Signal Transduction Wnt Proteins - physiology |
| title | CpG island methylation and expression of the secreted frizzled- related protein gene family in chronic lymphocytic leukemia |
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