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
2011 Impact Factor: 6.425
2011 SCImago Journal Rankings: 0.541
DOIhttp://dx.doi.org/10.1093/annonc/mdl035
ISI Accession Number IDWOS:000237174200017
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 6.425
2011 SCImago Journal Rankings: 0.541
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
Author Affiliations
  1. Università degli Studi di Palermo
  2. University of Western Australia