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Article: Functional categories of TP53 mutation in colorectal cancer: Results of an International Collaborative Study
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TitleFunctional categories of TP53 mutation in colorectal cancer: Results of an International Collaborative Study
 
AuthorsIacopetta, B1 2
Russo, A1
Bazan, V1
Dardanoni, G1
Gebbia, N1
Soussi, T1
Kerr, D1
Elsaleh, H1
Soong, R1
Kandioler, D1
Janschek, E1
Kappel, S1
Lung, M1
Leung, CSS1
Ko, JM1
Yuen, S1
Ho, J1
Leung, SY1
Crapez, E1
Duffour, J1
Ychou, M1
Leahy, DT1
O'Donoghue, DP1
Agnese, V1
Cascio, S1
Di Fede, G1
ChiecoBianchi, L1
Bertorelle, R1
Belluco, C1
Giaretti, W1
Castagnola, P1
Ricevuto, E1
Ficorella, C1
Bosari, S1
Arizzi, CD1
Miyaki, M1
Onda, M1
Kampman, E1
Diergaarde, B1
Royds, J1
Lothe, RA1
Diep, CB1
Meling, GI1
Ostrowski, J1
Trzeciak, L1
GuzińskaUstymowicz, K1
Zalewski, B1
Capellá, GM1
Moreno, V1
Peinado, MA1
Lönnroth, C1
Lundholm, K1
Sun, XF1
Jansson, A1
Bouzourene, H1
Hsieh, LL1
Tang, R1
Smith, DR1
AllenMersh, TG1
Khan, ZAJ1
Shorthouse, AJ1
Silverman, ML1
Kato, S1
Ishioka, C1
 
KeywordsChemotherapy
Colorectal cancer
Mutation
Prognosis
TP53
Transactivational ability
 
Issue Date2006
 
PublisherOxford University Press. The Journal's web site is located at http://annonc.oxfordjournals.org/
 
CitationAnnals Of Oncology, 2006, v. 17 n. 5, p. 842-847 [How to Cite?]
DOI: http://dx.doi.org/10.1093/annonc/mdl035
 
AbstractBackground: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (≤20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. Materials and methods: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. Results: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. Conclusions: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease. © 2006 Oxford University Press.
 
ISSN0923-7534
2013 Impact Factor: 6.578
 
DOIhttp://dx.doi.org/10.1093/annonc/mdl035
 
ISI Accession Number IDWOS:000237174200017
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorIacopetta, B
 
dc.contributor.authorRusso, A
 
dc.contributor.authorBazan, V
 
dc.contributor.authorDardanoni, G
 
dc.contributor.authorGebbia, N
 
dc.contributor.authorSoussi, T
 
dc.contributor.authorKerr, D
 
dc.contributor.authorElsaleh, H
 
dc.contributor.authorSoong, R
 
dc.contributor.authorKandioler, D
 
dc.contributor.authorJanschek, E
 
dc.contributor.authorKappel, S
 
dc.contributor.authorLung, M
 
dc.contributor.authorLeung, CSS
 
dc.contributor.authorKo, JM
 
dc.contributor.authorYuen, S
 
dc.contributor.authorHo, J
 
dc.contributor.authorLeung, SY
 
dc.contributor.authorCrapez, E
 
dc.contributor.authorDuffour, J
 
dc.contributor.authorYchou, M
 
dc.contributor.authorLeahy, DT
 
dc.contributor.authorO'Donoghue, DP
 
dc.contributor.authorAgnese, V
 
dc.contributor.authorCascio, S
 
dc.contributor.authorDi Fede, G
 
dc.contributor.authorChiecoBianchi, L
 
dc.contributor.authorBertorelle, R
 
dc.contributor.authorBelluco, C
 
dc.contributor.authorGiaretti, W
 
dc.contributor.authorCastagnola, P
 
dc.contributor.authorRicevuto, E
 
dc.contributor.authorFicorella, C
 
dc.contributor.authorBosari, S
 
dc.contributor.authorArizzi, CD
 
dc.contributor.authorMiyaki, M
 
dc.contributor.authorOnda, M
 
dc.contributor.authorKampman, E
 
dc.contributor.authorDiergaarde, B
 
dc.contributor.authorRoyds, J
 
dc.contributor.authorLothe, RA
 
dc.contributor.authorDiep, CB
 
dc.contributor.authorMeling, GI
 
dc.contributor.authorOstrowski, J
 
dc.contributor.authorTrzeciak, L
 
dc.contributor.authorGuzińskaUstymowicz, K
 
dc.contributor.authorZalewski, B
 
dc.contributor.authorCapellá, GM
 
dc.contributor.authorMoreno, V
 
dc.contributor.authorPeinado, MA
 
dc.contributor.authorLönnroth, C
 
dc.contributor.authorLundholm, K
 
dc.contributor.authorSun, XF
 
dc.contributor.authorJansson, A
 
dc.contributor.authorBouzourene, H
 
dc.contributor.authorHsieh, LL
 
dc.contributor.authorTang, R
 
dc.contributor.authorSmith, DR
 
dc.contributor.authorAllenMersh, TG
 
dc.contributor.authorKhan, ZAJ
 
dc.contributor.authorShorthouse, AJ
 
dc.contributor.authorSilverman, ML
 
dc.contributor.authorKato, S
 
dc.contributor.authorIshioka, C
 
dc.date.accessioned2010-09-06T09:47:50Z
 
dc.date.available2010-09-06T09:47:50Z
 
dc.date.issued2006
 
dc.description.abstractBackground: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (≤20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. Materials and methods: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. Results: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. Conclusions: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease. © 2006 Oxford University Press.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationAnnals Of Oncology, 2006, v. 17 n. 5, p. 842-847 [How to Cite?]
DOI: http://dx.doi.org/10.1093/annonc/mdl035
 
dc.identifier.citeulike607473
 
dc.identifier.doihttp://dx.doi.org/10.1093/annonc/mdl035
 
dc.identifier.epage847
 
dc.identifier.hkuros116117
 
dc.identifier.isiWOS:000237174200017
 
dc.identifier.issn0923-7534
2013 Impact Factor: 6.578
 
dc.identifier.issue5
 
dc.identifier.openurl
 
dc.identifier.pmid16524972
 
dc.identifier.scopuseid_2-s2.0-33646183787
 
dc.identifier.spage842
 
dc.identifier.urihttp://hdl.handle.net/10722/88775
 
dc.identifier.volume17
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://annonc.oxfordjournals.org/
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofAnnals of Oncology
 
dc.relation.referencesReferences in Scopus
 
dc.rightsAnnals of Oncology. Copyright © Oxford University Press.
 
dc.subject.meshAdenocarcinoma - drug therapy - genetics - pathology
 
dc.subject.meshAged
 
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols - therapeutic use
 
dc.subject.meshColorectal Neoplasms - drug therapy - genetics - pathology
 
dc.subject.meshDNA Mutational Analysis
 
dc.subject.meshExons
 
dc.subject.meshFemale
 
dc.subject.meshFollow-Up Studies
 
dc.subject.meshHumans
 
dc.subject.meshInternational Agencies
 
dc.subject.meshMale
 
dc.subject.meshMiddle Aged
 
dc.subject.meshMutation
 
dc.subject.meshNeoplasm Invasiveness - genetics - pathology
 
dc.subject.meshNeoplasm Staging
 
dc.subject.meshSurvival Rate
 
dc.subject.meshTumor Suppressor Protein p53 - genetics
 
dc.subjectChemotherapy
 
dc.subjectColorectal cancer
 
dc.subjectMutation
 
dc.subjectPrognosis
 
dc.subjectTP53
 
dc.subjectTransactivational ability
 
dc.titleFunctional categories of TP53 mutation in colorectal cancer: Results of an International Collaborative Study
 
dc.typeArticle
 
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<contributor.author>Russo, A</contributor.author>
<contributor.author>Bazan, V</contributor.author>
<contributor.author>Dardanoni, G</contributor.author>
<contributor.author>Gebbia, N</contributor.author>
<contributor.author>Soussi, T</contributor.author>
<contributor.author>Kerr, D</contributor.author>
<contributor.author>Elsaleh, H</contributor.author>
<contributor.author>Soong, R</contributor.author>
<contributor.author>Kandioler, D</contributor.author>
<contributor.author>Janschek, E</contributor.author>
<contributor.author>Kappel, S</contributor.author>
<contributor.author>Lung, M</contributor.author>
<contributor.author>Leung, CSS</contributor.author>
<contributor.author>Ko, JM</contributor.author>
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<contributor.author>Ho, J</contributor.author>
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<contributor.author>Crapez, E</contributor.author>
<contributor.author>Duffour, J</contributor.author>
<contributor.author>Ychou, M</contributor.author>
<contributor.author>Leahy, DT</contributor.author>
<contributor.author>O&apos;Donoghue, DP</contributor.author>
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<contributor.author>Cascio, S</contributor.author>
<contributor.author>Di Fede, G</contributor.author>
<contributor.author>ChiecoBianchi, L</contributor.author>
<contributor.author>Bertorelle, R</contributor.author>
<contributor.author>Belluco, C</contributor.author>
<contributor.author>Giaretti, W</contributor.author>
<contributor.author>Castagnola, P</contributor.author>
<contributor.author>Ricevuto, E</contributor.author>
<contributor.author>Ficorella, C</contributor.author>
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<contributor.author>Diergaarde, B</contributor.author>
<contributor.author>Royds, J</contributor.author>
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<contributor.author>Capell&#225;, GM</contributor.author>
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<contributor.author>Peinado, MA</contributor.author>
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<contributor.author>Lundholm, K</contributor.author>
<contributor.author>Sun, XF</contributor.author>
<contributor.author>Jansson, A</contributor.author>
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<contributor.author>Hsieh, LL</contributor.author>
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<date.issued>2006</date.issued>
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<identifier.uri>http://hdl.handle.net/10722/88775</identifier.uri>
<description.abstract>Background: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (&#8804;20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. Materials and methods: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. Results: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P &lt; 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes&apos; stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P &lt; 0.001). Patients with Dukes&apos; C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. Conclusions: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease. &#169; 2006 Oxford University Press.</description.abstract>
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<rights>Annals of Oncology. Copyright &#169; Oxford University Press.</rights>
<subject>Chemotherapy</subject>
<subject>Colorectal cancer</subject>
<subject>Mutation</subject>
<subject>Prognosis</subject>
<subject>TP53</subject>
<subject>Transactivational ability</subject>
<subject.mesh>Adenocarcinoma - drug therapy - genetics - pathology</subject.mesh>
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<subject.mesh>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject.mesh>
<subject.mesh>Colorectal Neoplasms - drug therapy - genetics - pathology</subject.mesh>
<subject.mesh>DNA Mutational Analysis</subject.mesh>
<subject.mesh>Exons</subject.mesh>
<subject.mesh>Female</subject.mesh>
<subject.mesh>Follow-Up Studies</subject.mesh>
<subject.mesh>Humans</subject.mesh>
<subject.mesh>International Agencies</subject.mesh>
<subject.mesh>Male</subject.mesh>
<subject.mesh>Middle Aged</subject.mesh>
<subject.mesh>Mutation</subject.mesh>
<subject.mesh>Neoplasm Invasiveness - genetics - pathology</subject.mesh>
<subject.mesh>Neoplasm Staging</subject.mesh>
<subject.mesh>Survival Rate</subject.mesh>
<subject.mesh>Tumor Suppressor Protein p53 - genetics</subject.mesh>
<title>Functional categories of TP53 mutation in colorectal cancer: Results of an International Collaborative Study</title>
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Author Affiliations
  1. Università degli Studi di Palermo
  2. University of Western Australia