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Article: Chromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutation

TitleChromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutation
Authors
KeywordsChromosomal instability
Colon carcinoma
Glioma
Microsatellite instability
p53 mutation
Turcot's syndrome
Issue Date2000
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2000, v. 19 n. 35, p. 4079-4083 How to Cite?
AbstractWe have previously reported high-frequency microsatellite instability (MSI-H) and germ-line mismatch repair gene mutation in patients with unusually young onset of high-grade glioma. Some of these patients developed metachronous MSI-H colorectal cancer and conformed to the diagnosis of Turcot's syndrome. Frameshift mutation of TGFβRII was present in all the colorectal carcinomas but not in brain tumours. We further characterized the genetic pathways of tumour evolution in these metachronous gliomas and colorectal carcinomas. All MSI-H glioblastomas had inactivation of both alleles of the p53 gene and showed over-expression of the p53 protein while none of the colorectal carcinomas had p53 mutation or protein over-expression. Flow cytometry and comparative genomic hybridization revealed that all glioblastomas were chromosomal unstable with aneuploid DNA content, and with a variable number of chromosomal arm aberrations. In contrast, the colorectal carcinomas had diploid or near-diploid DNA content with few chromosomal arm aberrations. The pattern of chromosomal aberrations in the two organs was different. Loss of 9p was consistently observed in all glioblastomas but not in colorectal carcinomas. Epidermal growth factor receptor amplification was absent in all glioblastomas and colorectal carcinomas. Our results suggest that both the frequency of p53 mutation and its effects differ greatly in the two organs. Following loss of mismatch repair function, p53 inactivation and chromosomal instability are not necessary for development of colorectal carcinoma, but are required for genesis of glioblastoma.
Persistent Identifierhttp://hdl.handle.net/10722/88550
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorChan, TLen_HK
dc.contributor.authorChan, ASen_HK
dc.contributor.authorHo, JWen_HK
dc.contributor.authorKwan, Ken_HK
dc.contributor.authorFan, YWen_HK
dc.contributor.authorHung, KNen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorWyllie, AHen_HK
dc.date.accessioned2010-09-06T09:44:50Z-
dc.date.available2010-09-06T09:44:50Z-
dc.date.issued2000en_HK
dc.identifier.citationOncogene, 2000, v. 19 n. 35, p. 4079-4083en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88550-
dc.description.abstractWe have previously reported high-frequency microsatellite instability (MSI-H) and germ-line mismatch repair gene mutation in patients with unusually young onset of high-grade glioma. Some of these patients developed metachronous MSI-H colorectal cancer and conformed to the diagnosis of Turcot's syndrome. Frameshift mutation of TGFβRII was present in all the colorectal carcinomas but not in brain tumours. We further characterized the genetic pathways of tumour evolution in these metachronous gliomas and colorectal carcinomas. All MSI-H glioblastomas had inactivation of both alleles of the p53 gene and showed over-expression of the p53 protein while none of the colorectal carcinomas had p53 mutation or protein over-expression. Flow cytometry and comparative genomic hybridization revealed that all glioblastomas were chromosomal unstable with aneuploid DNA content, and with a variable number of chromosomal arm aberrations. In contrast, the colorectal carcinomas had diploid or near-diploid DNA content with few chromosomal arm aberrations. The pattern of chromosomal aberrations in the two organs was different. Loss of 9p was consistently observed in all glioblastomas but not in colorectal carcinomas. Epidermal growth factor receptor amplification was absent in all glioblastomas and colorectal carcinomas. Our results suggest that both the frequency of p53 mutation and its effects differ greatly in the two organs. Following loss of mismatch repair function, p53 inactivation and chromosomal instability are not necessary for development of colorectal carcinoma, but are required for genesis of glioblastoma.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.subjectChromosomal instabilityen_HK
dc.subjectColon carcinomaen_HK
dc.subjectGliomaen_HK
dc.subjectMicrosatellite instabilityen_HK
dc.subjectp53 mutationen_HK
dc.subjectTurcot's syndromeen_HK
dc.subject.meshAdenocarcinoma - genetics - pathologyen_HK
dc.subject.meshAdulten_HK
dc.subject.meshBase Pair Mismatch - geneticsen_HK
dc.subject.meshBrain Neoplasms - genetics - pathologyen_HK
dc.subject.meshCell Transformation, Neoplastic - geneticsen_HK
dc.subject.meshChromosome Aberrationsen_HK
dc.subject.meshChromosome Deletionen_HK
dc.subject.meshChromosomes, Human, Pair 9 - geneticsen_HK
dc.subject.meshCodon - geneticsen_HK
dc.subject.meshColorectal Neoplasms - genetics - pathologyen_HK
dc.subject.meshDNA Repair - geneticsen_HK
dc.subject.meshDNA, Neoplasm - geneticsen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshGene Amplificationen_HK
dc.subject.meshGene Expression Regulation, Neoplasticen_HK
dc.subject.meshGenes, p53en_HK
dc.subject.meshGlioblastoma - genetics - pathologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMicrosatellite Repeatsen_HK
dc.subject.meshNeoplasm Proteins - biosynthesisen_HK
dc.subject.meshNeoplasms, Second Primary - genetics - pathologyen_HK
dc.subject.meshNeoplastic Syndromes, Hereditary - genetics - pathologyen_HK
dc.subject.meshNucleic Acid Hybridizationen_HK
dc.subject.meshOrgan Specificityen_HK
dc.subject.meshPloidiesen_HK
dc.subject.meshReceptor, Epidermal Growth Factor - geneticsen_HK
dc.subject.meshSyndromeen_HK
dc.subject.meshTumor Suppressor Protein p53 - biosynthesisen_HK
dc.titleChromosomal instability and p53 inactivation are required for genesis of glioblastoma but not for colorectal cancer in patients with germline mismatch repair gene mutationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=19&spage=4079&epage=4083&date=2000&atitle=Chromosomal+instability+and+p53+inactivation+are+required+for+genesis+of+glioblastoma+but+not+for+colorectal+cancer+in+patients+with+germline+mismatch+repair+gene+mutationen_HK
dc.identifier.emailLeung, SY: suetyi@hku.hken_HK
dc.identifier.emailChan, TL: tlchan@hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid10962567-
dc.identifier.scopuseid_2-s2.0-0034680035en_HK
dc.identifier.hkuros56460en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034680035&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume19en_HK
dc.identifier.issue35en_HK
dc.identifier.spage4079en_HK
dc.identifier.epage4083en_HK
dc.identifier.isiWOS:000088825300016-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridYuen, ST=7103160927en_HK
dc.identifier.scopusauthoridChan, TL=7402687537en_HK
dc.identifier.scopusauthoridChan, AS=7403168075en_HK
dc.identifier.scopusauthoridHo, JW=25925854200en_HK
dc.identifier.scopusauthoridKwan, K=7006405778en_HK
dc.identifier.scopusauthoridFan, YW=7403492523en_HK
dc.identifier.scopusauthoridHung, KN=7202728375en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridWyllie, AH=35474548100en_HK

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