Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study

Iacopetta, Barry; Russo, Antonio; Bazan, Viviana; Dardanoni, Gabriella; Gebbia, Nicola; Soussi, Thierry; Kerr, David; Elsaleh, Hany; Soong, Richie; Kandioler, Daniela; Janschek, Elisabeth; Kappel, Sonja; Lung, ML; Leung, C S; Ko, Josephine Mun Yee; Yuen, Siu Tsan; Ho, Jar-Yi; Leung, SC; Lopez-Crapez, Evelyne; Duffour, Jacqueline; Ychou, Marc; Leahy, Dorothy; O’Donoghue, Diarmuid; Agnese, Valentina; Cascio, Sandra; Fede, Gaetana Di; Chieco‐Bianchi, Luigi; Bertorelle, Roberta; Belluco, Claudio; Giaretti, Walter; Castagnola, Patrizio; Ricevuto, Enrico; Ficorella, Corrado; Bòsari, Silvano; Arizzi, Carmelo; Miyaki, Michiko; Onda, Masamitsu; Kampman, Ellen; Diergaarde, Brenda; Royds, Janice A.; Lothe, Ragnhild; Diep, Chieu B.; Meling, Gunn Iren; Ostrowski, J.L.; Trzeciak, Lech; Guzińska‐Ustymowicz, Katarzyna; Zalewski, Bogdan; Capellà, Gabriel; Moreno, Vı́ctor; Peinado, Miguel A.; Lönnroth, Christina; Lundholm, Kent; Sun, Xiao‐Feng; Jansson, Agneta; Bouzourène, Hanifa; Hsieh, Ling‐Ling; Tang, Reiping; Smith, Duncan R.; Allen-Mersh, T G; Khan, Zahra; Shorthouse, A. J.; Silverman, Mark L.; Kato, Shunsuke; Ishioka, Chikashi

doi:10.1093/annonc/mdl035

Cited by 99 publications

(65 citation statements)

References 12 publications

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“…3 The 5-year overall survival (OS) was 63%, with a median follow-up of 54.6 months. A clear prognostic value of the stage was observed in this series (see Supplemental Figure S1 at http://ajp.amjpathol.org).…”

Section: Clinical Datamentioning

confidence: 99%

“…In a large cohort of colorectal carcinomas published by the TP53-CRC Collaborative Study Group, this prognostic impact seems intricate and depends on tumor site, type of mutation, adjuvant therapy, and stage of the disease. 3,4 Posttranslational modifications of the p53 protein, such as ubiquitination, phosphorylation, and acetylation, contribute to p53 activity regulation, leading to protein stabilization, conformational changes, and modifications of its affinity for DNA and its interaction with transcriptional coactivator complexes. 5 As a result, the molecular modulators of p53 could play a significant role by influencing the p53-dependent responses in tumor cells and altering the prognostic significance of the p53 genetic status of the tumor.…”

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confidence: 99%

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Tissue Microarray Cytometry Reveals Positive Impact of Homeodomain Interacting Protein Kinase 2 in Colon Cancer Survival Irrespective of p53 Function

Soubeyran

Mahouche

Grigoletto

et al. 2011

The American Journal of Pathology

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The human p53 gene is a tumor suppressor mutated in half of colon cancers. Although p53 function appears important for proliferation arrest and apoptosis induced by cancer therapeutics, the prognostic significance of p53 mutations remains elusive. This suggests that p53 function is modulated at a posttranslational level and that dysfunctions affecting its modulators can have a prognostic impact. Among p53 modulators, homeodomain interacting protein kinase (HIPK) 2 emerges as a candidate "switch" governing p53 transition from a cytostatic to a proapoptotic function. Thus, we investigated the possible prognostic role of HIPK2 on a retrospective series of 80 colon cancer cases by setting up a multiplexed cytometric approach capable of exploring correlative protein expression at the single tumor cell level on TMA. Crossing the data with quantitative PCR and p53 gene sequencing and p53 functional assays, we observed the following: despite a strong impact on p21 transcription, the presence of disabling p53 mutations has no prognostic value, and the increased expression of the HIPK2 protein in tumor cells compared with paired normal tissue cells has a strong impact on survival. Unexpectedly, HIPK2 effect does not appear to be mediated by p53 function because it is also observed in p53-disabling mutated backgrounds. Thus, our results point to a prominent and p53-independent role of HIPK2 in colon cancer survival.

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Section: Clinical Datamentioning

confidence: 99%

mentioning

confidence: 99%

Tissue Microarray Cytometry Reveals Positive Impact of Homeodomain Interacting Protein Kinase 2 in Colon Cancer Survival Irrespective of p53 Function

Soubeyran

Mahouche

Grigoletto

et al. 2011

The American Journal of Pathology

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“…Diep et al (2003) showed that TP53 mutations affecting the L3 zinc-binding domain and lower survival rate in the subclassification of Dukes' B and C patients and may have an impact on the ideal treatment strategy. However, the prognostic role of TP53-inactivating mutations is still in question (Iacopetta et al, 2006). Similarly, the impacts of epidermal growth factor receptor (EGFR) over-expression, loss of heterozygosity in chromosome 18q, somatic adenomatous polyposis coli (APC), and KRAS mutations on survival remain unclear (Diep et al, 2003;Spano et al, 2005;Walther et al, 2009).…”

Section: Molecular Markersmentioning

confidence: 99%

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

Jiang

et al. 2012

J. Zhejiang Univ. Sci. B

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Abstract:Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide. Although we have made steady progress in chemotherapy and targeted therapy, evidence suggests that the majority of patients undergoing drug therapy experience severe, debilitating, and even lethal adverse drug events which considerably outweigh the benefits. The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments. Prognostic and predictive biomarkers have been the subjects of many published papers, but few have been widely incorporated into clinical practice. Here, we want to review recent biomarker data related to colorectal cancer, which may have been ready for clinical use.

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“…Many studies on CRC patients have shown evidence of the prognostic value of TP53 mutations/loss of function and its association with worse survival. [28][29][30] No robust evidence or consensus about predictive role of p53 in relation to treatment is yet available, and therefore p53 is not routinely used in clinical practice.…”

Section: Genetic Alterations In Tumor Tissuesmentioning

confidence: 99%

Pharmacogenetics and biomarkers in colorectal cancer

2009

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The prognosis of patients with colorectal cancer (CRC) is affected by various factors at the time of diagnosis, including location of the tumor, gender, age and overall performance status of the patient. Predicting response and limiting drug-induced toxicity for patients with CRC are also critical. Interpatient differences in tumor response and drug toxicity are common during chemotherapy. Genomic variability of key metabolic enzyme complexes, drug targets and drug transport molecules are important contributing factors. At present, there is inconsistent and rather low use of pharmacogenetic testing in the clinical setting because of a lack of robust evidence or of resources. Patients' selection and tailored treatments by the introduction of genetic testing will hopefully allow better response prediction and limit drug-induced toxicity leading to improved patient outcomes in the most cost-effective way. Here, we review the main genetic alterations observed in familial and sporadic CRC and their associations with the metabolism, efficacy and toxicities of drugs used in this disease.

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Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study

Abstract: 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.

Cited by 99 publications

References 12 publications

Tissue Microarray Cytometry Reveals Positive Impact of Homeodomain Interacting Protein Kinase 2 in Colon Cancer Survival Irrespective of p53 Function

Tissue Microarray Cytometry Reveals Positive Impact of Homeodomain Interacting Protein Kinase 2 in Colon Cancer Survival Irrespective of p53 Function

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

Pharmacogenetics and biomarkers in colorectal cancer

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