1. Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study
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IACOPETTA B, RUSSO, Antonio, BAZAN, Viviana, DARDANONI G, GEBBIA, Nicolo', SOUSSI T, KERR D, ELSALEH H, SOONG R, KANDIOLER D, JANSCHEK E, KAPPEL S, LUNG M, LEUNG CS, KO JM, YUEN S, HO J, LEUNG SY, CRAPEZ E, DUFFOUR J, YCHOU M, LEAHY DT, O'DONOGHUE DP, AGNESE, Valentina, CASCIO, Sandra, DI FEDE, Gaetana, CHIECO BIANCHI L, BERTORELLE R, BELLUCO C, GIARETTI W, CASTAGNOLA P, RICEVUTO E, FICORELLA C, BOSARI S, ARIZZI, Carmela Rosaria, MIYAKI, M, ONDA M, KAMPMAN E, DIERGAARDE B, ROYDS J, LOTHE RA, DIEP CB, MELING GI, OSTROWSKI J, TRZECIAK L, GUZINSKA USTYMOWICZ K, ZALEWSKI B, CAPELLA GM, MORENO, V, PEINADO MA, LONNROTH C, LUNDHOLM K, SUN XF, JANSSON A, BOUZOURENE H, HSIEH, LL, TANG R, SMITH DR, ALLEN MERSH TG, KHAN ZA, SHORTHOUSE AJ, SILVERMAN ML, KATO, S, ISHIOKA C, TP CRC COLLABORATIVE GROUP, IACOPETTA B, RUSSO A, BAZAN V, DARDANONI G, GEBBIA N, SOUSSI T, KERR D, ELSALEH H, SOONG R, KANDIOLER D, JANSCHEK E, KAPPEL S, LUNG M, LEUNG CS, KO JM, YUEN S, HO J, LEUNG SY, CRAPEZ E, DUFFOUR J, YCHOU M, LEAHY DT, O'DONOGHUE DP, AGNESE V, CASCIO S, DI FEDE G, CHIECO-BIANCHI L, BERTORELLE R, BELLUCO C, GIARETTI W, CASTAGNOLA P, RICEVUTO E, FICORELLA C, BOSARI S, ARIZZI CD, MIYAKI, ONDA M, KAMPMAN E, DIERGAARDE B, ROYDS J, LOTHE RA, DIEP CB, MELING GI, OSTROWSKI J, TRZECIAK L, GUZINSKA-USTYMOWICZ K, ZALEWSKI B, CAPELLA GM, MORENO, PEINADO MA, LONNROTH C, LUNDHOLM K, SUN XF, JANSSON A, BOUZOURENE H, HSIEH, LL, TANG R, SMITH DR, ALLEN-MERSH TG, KHAN ZA, SHORTHOUSE AJ, SILVERMAN ML, KATO, ISHIOKA C, and TP-CRC COLLABORATIVE GROUP
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Oncology ,p53 ,Male ,Nutrition and Disease ,binding domains ,Lymphovascular invasion ,Colorectal cancer ,DNA Mutational Analysis ,Aetiology, screening and detection [ONCOL 5] ,Gene mutation ,medicine.disease_cause ,Transactivation ,Voeding en Ziekte ,Antineoplastic Combined Chemotherapy Protocols ,Determinants in Health and Disease [EBP 1] ,transcriptional activity ,Mutation ,Hematology ,Exons ,Middle Aged ,Survival Rate ,Adenocarcinoma ,Female ,Colorectal Neoplasms ,medicine.medical_specialty ,chemotherapy, colorectal cancer, mutation, prognosis, TP53, transactivational ability ,Molecular epidemiology [NCEBP 1] ,Breast cancer ,Translational research [ONCOL 3] ,Interventional oncology [UMCN 1.5] ,Internal medicine ,medicine ,Humans ,Neoplasm Invasiveness ,Survival rate ,neoplasms ,breast-cancer ,VLAG ,Aged ,Neoplasm Staging ,Hereditary cancer and cancer-related syndromes [ONCOL 1] ,business.industry ,International Agencies ,medicine.disease ,Immunology ,Tumor Suppressor Protein p53 ,business ,Follow-Up Studies - Abstract
Item does not contain fulltext 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 (< or=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.
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- 2006
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