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Article: Ubiquitous Aberrant RASSF1A Promoter Methylation in Childhood Neoplasia

TitleUbiquitous Aberrant RASSF1A Promoter Methylation in Childhood Neoplasia
Authors
Issue Date2004
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2004, v. 10 n. 3, p. 994-1002 How to Cite?
AbstractPURPOSE AND EXPERIMENTAL DESIGN: The role of RASSF1A has been elucidated recently in regulating apoptosis and cell cycle progression by inhibiting cyclin D1 accumulation. Aberrant RASSF1A promoter methylation has been found frequently in multiple adult cancer types. Using methylation-specific PCR and reverse transcription-PCR, we investigated epigenetic deregulation of RASSF1A in primary tumors, adjacent nontumor tissues, secondary metastases, peripheral blood cells, and plasma samples from children with 18 different cancer types, in association with their clinicopathologic features. RESULTS: Regardless of the tumor size, ubiquitous RASSF1A promoter methylation was found in 67% (16 of 24) of pediatric tumors, including neuroblastoma, thyroid carcinoma, hepatocellular carcinoma, pancreatoblastoma, adrenocortical carcinoma, Wilms' tumor, Burkitt's lymphoma, and T-cell lymphoma. A majority (75%) of pediatric cancer patients with tumoral RASSF1A methylation was male. Methylated RASSF1A alleles were also detected in 4 of 13 adjacent nontumor tissues, suggesting that this epigenetic change is potentially an early and critical event in childhood neoplasia. RASSF1A promoter methylation found in 92% (11 of 12) of cell lines largely derived from pediatric cancer patients was significantly associated with transcriptional silencing/repression. After demethylation treatment with 5-aza-2'-deoxycytidine, transcriptional reactivation was shown in KELLY, RD, and Namalwa cell lines as analyzed by reverse transcription-PCR. For the first time, RASSF1A methylation was detected in 54% (7 of 13), 40% (4 of 10), and 9% (1 of 11) of buffy coat samples collected before, during, and after treatment, correspondingly, from pediatric patients with neuroblastoma, thyroid carcinoma, hepatocellular carcinoma, rhabdomyosarcoma, Burkitt's lymphoma, T-cell lymphoma, or acute lymphoblastic leukemia. Concordantly, RASSF1A methylation was found during treatment in plasma of the same patients, suggesting cell death and good response to chemotherapy. CONCLUSIONS: RASSF1A methylation in tumor or buffy coat did not correlate strongly with age, tumor size, recurrence/metastasis, or overall survival in this cohort of pediatric cancer patients. Of importance, epigenetic inactivation of RASSF1A may potentially be crucial in pediatric tumor initiation.
Persistent Identifierhttp://hdl.handle.net/10722/83481
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, IHNen_HK
dc.contributor.authorChan, Jen_HK
dc.contributor.authorWong, Jen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T08:41:33Z-
dc.date.available2010-09-06T08:41:33Z-
dc.date.issued2004en_HK
dc.identifier.citationClinical Cancer Research, 2004, v. 10 n. 3, p. 994-1002en_HK
dc.identifier.issn1078-0432en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83481-
dc.description.abstractPURPOSE AND EXPERIMENTAL DESIGN: The role of RASSF1A has been elucidated recently in regulating apoptosis and cell cycle progression by inhibiting cyclin D1 accumulation. Aberrant RASSF1A promoter methylation has been found frequently in multiple adult cancer types. Using methylation-specific PCR and reverse transcription-PCR, we investigated epigenetic deregulation of RASSF1A in primary tumors, adjacent nontumor tissues, secondary metastases, peripheral blood cells, and plasma samples from children with 18 different cancer types, in association with their clinicopathologic features. RESULTS: Regardless of the tumor size, ubiquitous RASSF1A promoter methylation was found in 67% (16 of 24) of pediatric tumors, including neuroblastoma, thyroid carcinoma, hepatocellular carcinoma, pancreatoblastoma, adrenocortical carcinoma, Wilms' tumor, Burkitt's lymphoma, and T-cell lymphoma. A majority (75%) of pediatric cancer patients with tumoral RASSF1A methylation was male. Methylated RASSF1A alleles were also detected in 4 of 13 adjacent nontumor tissues, suggesting that this epigenetic change is potentially an early and critical event in childhood neoplasia. RASSF1A promoter methylation found in 92% (11 of 12) of cell lines largely derived from pediatric cancer patients was significantly associated with transcriptional silencing/repression. After demethylation treatment with 5-aza-2'-deoxycytidine, transcriptional reactivation was shown in KELLY, RD, and Namalwa cell lines as analyzed by reverse transcription-PCR. For the first time, RASSF1A methylation was detected in 54% (7 of 13), 40% (4 of 10), and 9% (1 of 11) of buffy coat samples collected before, during, and after treatment, correspondingly, from pediatric patients with neuroblastoma, thyroid carcinoma, hepatocellular carcinoma, rhabdomyosarcoma, Burkitt's lymphoma, T-cell lymphoma, or acute lymphoblastic leukemia. Concordantly, RASSF1A methylation was found during treatment in plasma of the same patients, suggesting cell death and good response to chemotherapy. CONCLUSIONS: RASSF1A methylation in tumor or buffy coat did not correlate strongly with age, tumor size, recurrence/metastasis, or overall survival in this cohort of pediatric cancer patients. Of importance, epigenetic inactivation of RASSF1A may potentially be crucial in pediatric tumor initiation.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/en_HK
dc.relation.ispartofClinical Cancer Researchen_HK
dc.subject.meshCyclin D1 - biosynthesis-
dc.subject.meshDNA Methylation-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshNeoplasms - genetics-
dc.subject.meshTumor Suppressor Proteins - genetics-
dc.titleUbiquitous Aberrant RASSF1A Promoter Methylation in Childhood Neoplasiaen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, IHN: ihnwong@hkucc.hku.hken_HK
dc.identifier.emailWong, J: jwong@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hk-
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-0378-3-
dc.identifier.pmid14871978-
dc.identifier.scopuseid_2-s2.0-1042301960-
dc.identifier.hkuros85949en_HK
dc.identifier.volume10-
dc.identifier.issue3-
dc.identifier.spage994-
dc.identifier.epage1002-
dc.identifier.isiWOS:000188982700024-
dc.publisher.placeUnited States-

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