Methylation similarities of two CpG sites within exon 5 of human H19 between normal tissues and testicular germ cell tumours of adolescents and adults, without correlation with allelic and total level of expression
Testicular germ cell tumours (TGCTs) of adolescents and adults morphologically mimic different stages of embryogenesis. Established cell lines of these cancers are used as informative models to study early development. We found that, in contrast to normal development, TGCTs show a consistent biallel...
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| Veröffentlicht in: | British journal of cancer 1997, Vol.76 (6), p.725-733 |
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| container_title | British journal of cancer |
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| creator | Gillis, AJM Verkerk, AJMH Dekker, MC van Gurp, RJHLM Oosterhuis, JWJ Looijenga, LHJ |
| description | Testicular germ cell tumours (TGCTs) of adolescents and adults morphologically mimic different stages of embryogenesis. Established cell lines of these cancers are used as informative models to study early development. We found that, in contrast to normal development, TGCTs show a consistent biallelic expression of imprinted genes, including H19, irrespective of histology. Methylation of particular cytosine residues of H19 correlates with inhibition of expression, which has not been studied in TGCTs thus far. We investigated the methylation status of two CpG sites within the 3' region of H19 (exon 5: positions 3321 and 3324) both in normal tissues as well as in TGCTs. To obtain quantitative data of these specific sites, the ligation-mediated polymerase chain reaction technique, instead of Southern blot analysis, was applied. The results were compared with the allelic status and the total level of expression of this gene. Additionally, the undifferentiated cells and differentiated derivatives of the TGCT-derived cell line NT2-D1 were analysed. While peripheral blood showed no H19 expression and complete methylation, a heterogeneous but consistent pattern of methylation and level of expression was found in the other normal tissues, without a correlation between the two. The separate histological entities of TGCTs resembled the pattern of their nonmalignant tissues. While the CpG sites remained completely methylated in NT2-D1, H19 expression was induced upon differentiation. These data indicate that methylation of the CpG sites within exon 5 of H19 is tissue dependent, without regulating allelic status and/or total level of expression. Of special note is the finding that, also regarding methylation of these particular sites of H19, TGCTs mimic their non-malignant counterparts, in spite of their consistent biallelic expression. |
| doi_str_mv | 10.1038/bjc.1997.453 |
| format | Article |
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Established cell lines of these cancers are used as informative models to study early development. We found that, in contrast to normal development, TGCTs show a consistent biallelic expression of imprinted genes, including H19, irrespective of histology. Methylation of particular cytosine residues of H19 correlates with inhibition of expression, which has not been studied in TGCTs thus far. We investigated the methylation status of two CpG sites within the 3' region of H19 (exon 5: positions 3321 and 3324) both in normal tissues as well as in TGCTs. To obtain quantitative data of these specific sites, the ligation-mediated polymerase chain reaction technique, instead of Southern blot analysis, was applied. The results were compared with the allelic status and the total level of expression of this gene. Additionally, the undifferentiated cells and differentiated derivatives of the TGCT-derived cell line NT2-D1 were analysed. While peripheral blood showed no H19 expression and complete methylation, a heterogeneous but consistent pattern of methylation and level of expression was found in the other normal tissues, without a correlation between the two. The separate histological entities of TGCTs resembled the pattern of their nonmalignant tissues. While the CpG sites remained completely methylated in NT2-D1, H19 expression was induced upon differentiation. These data indicate that methylation of the CpG sites within exon 5 of H19 is tissue dependent, without regulating allelic status and/or total level of expression. Of special note is the finding that, also regarding methylation of these particular sites of H19, TGCTs mimic their non-malignant counterparts, in spite of their consistent biallelic expression.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.1997.453</identifier><identifier>PMID: 9310237</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adolescent ; Adult ; Alleles ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; DNA Ligases - metabolism ; DNA Methylation ; DNA, Neoplasm - genetics ; Drug Resistance ; Epidemiology ; Exons ; experimental-oncology ; Gene Expression Regulation, Neoplastic ; General aspects ; Germinoma - genetics ; Humans ; Male ; Medical sciences ; Molecular Medicine ; Muscle Proteins - genetics ; Oncology ; Polymerase Chain Reaction - methods ; RNA, Long Noncoding ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; RNA, Untranslated ; Testicular Neoplasms - genetics ; Tumor Cells, Cultured</subject><ispartof>British journal of cancer, 1997, Vol.76 (6), p.725-733</ispartof><rights>Cancer Research Campaign 1997</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-ef742065630dc1f4586ed60e92fccf1bd995d646a90e5130f36f7a723ac6a2d63</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228033/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228033/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4022,27922,27923,27924,41487,42556,51318,53790,53792</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2797565$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9310237$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gillis, AJM</creatorcontrib><creatorcontrib>Verkerk, AJMH</creatorcontrib><creatorcontrib>Dekker, MC</creatorcontrib><creatorcontrib>van Gurp, RJHLM</creatorcontrib><creatorcontrib>Oosterhuis, JWJ</creatorcontrib><creatorcontrib>Looijenga, LHJ</creatorcontrib><title>Methylation similarities of two CpG sites within exon 5 of human H19 between normal tissues and testicular germ cell tumours of adolescents and adults, without correlation with allelic and total level of expression</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Testicular germ cell tumours (TGCTs) of adolescents and adults morphologically mimic different stages of embryogenesis. Established cell lines of these cancers are used as informative models to study early development. We found that, in contrast to normal development, TGCTs show a consistent biallelic expression of imprinted genes, including H19, irrespective of histology. Methylation of particular cytosine residues of H19 correlates with inhibition of expression, which has not been studied in TGCTs thus far. We investigated the methylation status of two CpG sites within the 3' region of H19 (exon 5: positions 3321 and 3324) both in normal tissues as well as in TGCTs. To obtain quantitative data of these specific sites, the ligation-mediated polymerase chain reaction technique, instead of Southern blot analysis, was applied. The results were compared with the allelic status and the total level of expression of this gene. Additionally, the undifferentiated cells and differentiated derivatives of the TGCT-derived cell line NT2-D1 were analysed. While peripheral blood showed no H19 expression and complete methylation, a heterogeneous but consistent pattern of methylation and level of expression was found in the other normal tissues, without a correlation between the two. The separate histological entities of TGCTs resembled the pattern of their nonmalignant tissues. While the CpG sites remained completely methylated in NT2-D1, H19 expression was induced upon differentiation. These data indicate that methylation of the CpG sites within exon 5 of H19 is tissue dependent, without regulating allelic status and/or total level of expression. Of special note is the finding that, also regarding methylation of these particular sites of H19, TGCTs mimic their non-malignant counterparts, in spite of their consistent biallelic expression.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>DNA Ligases - metabolism</subject><subject>DNA Methylation</subject><subject>DNA, Neoplasm - genetics</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Exons</subject><subject>experimental-oncology</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>General aspects</subject><subject>Germinoma - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molecular Medicine</subject><subject>Muscle Proteins - genetics</subject><subject>Oncology</subject><subject>Polymerase Chain Reaction - methods</subject><subject>RNA, Long Noncoding</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Untranslated</subject><subject>Testicular Neoplasms - genetics</subject><subject>Tumor Cells, Cultured</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkkFv1DAQhSMEKkvhxhXJB8SpWRw7ieMLUrWCtlIRFzhbXmfS9cqxF9vptn-U38Oku1pRiVOUeZ_fs2emKN5XdFlR3n1eb82yklIs64a_KBZVw1lZdUy8LBaUUlFSyejr4k1KW_yVtBNnxZnkFWVcLIo_3yFvHp3ONniS7GidjjZbSCQMJO8DWe2usJ6xsLd5Yz2BBySbWd5Mo_bkupJkDXkP4IkPcdSOZJvShCe07wmezNZMaEvuII7EgENgGsMUnzJ0HxwkAz4feN1PLqeLp7QwZWJCjHC831wj2jlw1hzMQ8Y4B_fgZi942EVICdG3xatBuwTvjt_z4te3rz9X1-Xtj6ub1eVtaeq6zSUMoma0bVpOe1MNddO10LcUJBuMGap1L2XTt3WrJYWm4nTg7SC0YFybVrO-5efFl4PvblqP0M_PiNqpXbSjjo8qaKueK95u1F24V4yxjnKOBp-OBjH8xp5lNdo090h7CFNSAifVdFQieHEATQwpRRhOIRVV8x4o3AM174HCPUD8w78XO8HHwaP-8ajrZLQbovbGphPGhBRN2yBWHrCEiscBqi0OzmNL_x_7Fzxw0OE</recordid><startdate>1997</startdate><enddate>1997</enddate><creator>Gillis, AJM</creator><creator>Verkerk, AJMH</creator><creator>Dekker, MC</creator><creator>van Gurp, RJHLM</creator><creator>Oosterhuis, JWJ</creator><creator>Looijenga, LHJ</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>1997</creationdate><title>Methylation similarities of two CpG sites within exon 5 of human H19 between normal tissues and testicular germ cell tumours of adolescents and adults, without correlation with allelic and total level of expression</title><author>Gillis, AJM ; Verkerk, AJMH ; Dekker, MC ; van Gurp, RJHLM ; Oosterhuis, JWJ ; Looijenga, LHJ</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-ef742065630dc1f4586ed60e92fccf1bd995d646a90e5130f36f7a723ac6a2d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>DNA Ligases - metabolism</topic><topic>DNA Methylation</topic><topic>DNA, Neoplasm - genetics</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Exons</topic><topic>experimental-oncology</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>General aspects</topic><topic>Germinoma - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Molecular Medicine</topic><topic>Muscle Proteins - genetics</topic><topic>Oncology</topic><topic>Polymerase Chain Reaction - methods</topic><topic>RNA, Long Noncoding</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Neoplasm - genetics</topic><topic>RNA, Untranslated</topic><topic>Testicular Neoplasms - genetics</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gillis, AJM</creatorcontrib><creatorcontrib>Verkerk, AJMH</creatorcontrib><creatorcontrib>Dekker, MC</creatorcontrib><creatorcontrib>van Gurp, RJHLM</creatorcontrib><creatorcontrib>Oosterhuis, JWJ</creatorcontrib><creatorcontrib>Looijenga, LHJ</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gillis, AJM</au><au>Verkerk, AJMH</au><au>Dekker, MC</au><au>van Gurp, RJHLM</au><au>Oosterhuis, JWJ</au><au>Looijenga, LHJ</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylation similarities of two CpG sites within exon 5 of human H19 between normal tissues and testicular germ cell tumours of adolescents and adults, without correlation with allelic and total level of expression</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>1997</date><risdate>1997</risdate><volume>76</volume><issue>6</issue><spage>725</spage><epage>733</epage><pages>725-733</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Testicular germ cell tumours (TGCTs) of adolescents and adults morphologically mimic different stages of embryogenesis. Established cell lines of these cancers are used as informative models to study early development. We found that, in contrast to normal development, TGCTs show a consistent biallelic expression of imprinted genes, including H19, irrespective of histology. Methylation of particular cytosine residues of H19 correlates with inhibition of expression, which has not been studied in TGCTs thus far. We investigated the methylation status of two CpG sites within the 3' region of H19 (exon 5: positions 3321 and 3324) both in normal tissues as well as in TGCTs. To obtain quantitative data of these specific sites, the ligation-mediated polymerase chain reaction technique, instead of Southern blot analysis, was applied. The results were compared with the allelic status and the total level of expression of this gene. Additionally, the undifferentiated cells and differentiated derivatives of the TGCT-derived cell line NT2-D1 were analysed. While peripheral blood showed no H19 expression and complete methylation, a heterogeneous but consistent pattern of methylation and level of expression was found in the other normal tissues, without a correlation between the two. The separate histological entities of TGCTs resembled the pattern of their nonmalignant tissues. While the CpG sites remained completely methylated in NT2-D1, H19 expression was induced upon differentiation. These data indicate that methylation of the CpG sites within exon 5 of H19 is tissue dependent, without regulating allelic status and/or total level of expression. Of special note is the finding that, also regarding methylation of these particular sites of H19, TGCTs mimic their non-malignant counterparts, in spite of their consistent biallelic expression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>9310237</pmid><doi>10.1038/bjc.1997.453</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Alleles Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research DNA Ligases - metabolism DNA Methylation DNA, Neoplasm - genetics Drug Resistance Epidemiology Exons experimental-oncology Gene Expression Regulation, Neoplastic General aspects Germinoma - genetics Humans Male Medical sciences Molecular Medicine Muscle Proteins - genetics Oncology Polymerase Chain Reaction - methods RNA, Long Noncoding RNA, Messenger - genetics RNA, Neoplasm - genetics RNA, Untranslated Testicular Neoplasms - genetics Tumor Cells, Cultured |
| title | Methylation similarities of two CpG sites within exon 5 of human H19 between normal tissues and testicular germ cell tumours of adolescents and adults, without correlation with allelic and total level of expression |
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