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Article: Frequent epigenetic inactivation of the RASSF1A tumor suppressor gene in Hodgkin's lymphoma

TitleFrequent epigenetic inactivation of the RASSF1A tumor suppressor gene in Hodgkin's lymphoma
Authors
KeywordsHodgkin's lymphoma
Hodgkin/Reed-Sternberg cells
Hypermethylation
RASSF1A
Tumor suppressor gene
Issue Date2004
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2004, v. 23 n. 6, p. 1326-1331 How to Cite?
AbstractEpigenetic inactivation of RASSF1A, a putative tumor suppressor with proapoptotic activity, is frequently observed in a number of solid tumors, including a variety of epithelial cancers, but has not been described in hematopoietic tumors. We have analysed the expression and methylation status of RASSF1A in Hodgkin's lymphoma (HL)-derived cell lines, primary HL tumors and serum samples from HL patients. RASSF1A transcription was detectable in only 2/ 6 HL cell lines. Methylation-specific PCR and bisulfite genomic sequencing revealed that the RASSF1A promoter was hypermethylated in all four RASSF1A-nonexpressing cell lines. 5-aza-2′-deoxycytidine treatment resulted in demethylation of the promoter and RASSF1A expression in these lines. Hypermethylation of RASSF1A was also detected in 34/52 (65%) primary HL tumors and in 2/22 serum samples from these patients. Microdissection of Hodgkin/ Reed-Sternberg (HRS) cells from several of these cases confirmed that the RASSF1A hypermethylation we detected in the analysis of whole tumor originated from the tumor cell population. Although hypermethylation of RASSF1A was detected in 5/6 non-Hodgkin's lymphoma (NHL)-derived cell lines, only rare primary NHL (1/10 of Burkitt's lymphoma, 1/12 of post-transplant lymphoma, 1/12 diffuse large B-cell lymphoma, 0/27 of nasal lymphoma, 0/8 follicular center cell lymphoma, 0/4 mantle cell lymphoma, 0/4 anaplastic large cell (Ki-1 +) lymphoma, 0/2 MALT lymphoma) showed hypermethylation of the promoter. No methylation was detected in any of the 14 normal PBMC. These results point to an important role for epigenetic silencing of RASSF1A in the pathogenesis of HL. Inactivation of RASSF1A could be one mechanism by which HRS cells escape the apoptosis that should occur following nonproductive immunoglobulin gene rearrangements.
Persistent Identifierhttp://hdl.handle.net/10722/88569
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMurray, PGen_HK
dc.contributor.authorQiu, GHen_HK
dc.contributor.authorFu, Len_HK
dc.contributor.authorWaites, ERen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.contributor.authorHeys, Den_HK
dc.contributor.authorAgathanggelou, Aen_HK
dc.contributor.authorLatif, Fen_HK
dc.contributor.authorGrundy, RGen_HK
dc.contributor.authorMann, JRen_HK
dc.contributor.authorStarczynski, Jen_HK
dc.contributor.authorCrocker, Jen_HK
dc.contributor.authorParkes, SEen_HK
dc.contributor.authorAmbinder, RFen_HK
dc.contributor.authorYoung, LSen_HK
dc.contributor.authorTao, Qen_HK
dc.date.accessioned2010-09-06T09:45:05Z-
dc.date.available2010-09-06T09:45:05Z-
dc.date.issued2004en_HK
dc.identifier.citationOncogene, 2004, v. 23 n. 6, p. 1326-1331en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88569-
dc.description.abstractEpigenetic inactivation of RASSF1A, a putative tumor suppressor with proapoptotic activity, is frequently observed in a number of solid tumors, including a variety of epithelial cancers, but has not been described in hematopoietic tumors. We have analysed the expression and methylation status of RASSF1A in Hodgkin's lymphoma (HL)-derived cell lines, primary HL tumors and serum samples from HL patients. RASSF1A transcription was detectable in only 2/ 6 HL cell lines. Methylation-specific PCR and bisulfite genomic sequencing revealed that the RASSF1A promoter was hypermethylated in all four RASSF1A-nonexpressing cell lines. 5-aza-2′-deoxycytidine treatment resulted in demethylation of the promoter and RASSF1A expression in these lines. Hypermethylation of RASSF1A was also detected in 34/52 (65%) primary HL tumors and in 2/22 serum samples from these patients. Microdissection of Hodgkin/ Reed-Sternberg (HRS) cells from several of these cases confirmed that the RASSF1A hypermethylation we detected in the analysis of whole tumor originated from the tumor cell population. Although hypermethylation of RASSF1A was detected in 5/6 non-Hodgkin's lymphoma (NHL)-derived cell lines, only rare primary NHL (1/10 of Burkitt's lymphoma, 1/12 of post-transplant lymphoma, 1/12 diffuse large B-cell lymphoma, 0/27 of nasal lymphoma, 0/8 follicular center cell lymphoma, 0/4 mantle cell lymphoma, 0/4 anaplastic large cell (Ki-1 +) lymphoma, 0/2 MALT lymphoma) showed hypermethylation of the promoter. No methylation was detected in any of the 14 normal PBMC. These results point to an important role for epigenetic silencing of RASSF1A in the pathogenesis of HL. Inactivation of RASSF1A could be one mechanism by which HRS cells escape the apoptosis that should occur following nonproductive immunoglobulin gene rearrangements.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectHodgkin's lymphomaen_HK
dc.subjectHodgkin/Reed-Sternberg cellsen_HK
dc.subjectHypermethylationen_HK
dc.subjectRASSF1Aen_HK
dc.subjectTumor suppressor geneen_HK
dc.titleFrequent epigenetic inactivation of the RASSF1A tumor suppressor gene in Hodgkin's lymphomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=23&issue=6&spage=1326&epage=1331&date=2004&atitle=Frequent+epigenetic+inactivation+of+the+RASSF1A+tumor+suppressor+gene+in+Hodgkin%27s+lymphomaen_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.onc.1207313en_HK
dc.identifier.scopuseid_2-s2.0-10744226221en_HK
dc.identifier.hkuros86082en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-10744226221&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume23en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1326en_HK
dc.identifier.epage1331en_HK
dc.identifier.isiWOS:000188892200019-
dc.publisher.placeUnited Kingdomen_HK

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