TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett's esophagus

Hamelin, Richard; Fléjou, J.-F.; Muzeau, Françoise; Potet, F; Laurent‐Puig, Pierre; Fékété, F; Thomas, Gilles

doi:10.1016/0016-5085(94)90225-9

Cited by 150 publications

(102 citation statements)

References 31 publications

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“…The mutation frequency determined in this investigation was considerably lower than reported in the general literature; nevertheless, two other studies documented comparably lower p53 mutation frequencies of 8 and 12% (also at codon 245) (Casson et al, 1991;Gonzalez et al, 1997). It is unlikely that just examining exons 5 -8 missed many mutations, as 490% of the mutations documented in a wide range of tumours are found within this region (Hamelin et al, 1994;www.iarc.fr). This discrepancy could be due to several factors.…”

Section: Discussioncontrasting

confidence: 56%

“…Hence, suggesting LOH of the p53 locus is an important change that develops early during Barrett's neoplastic progression. p53 mutations frequently arise in both Barrett's oesophagus and oesophageal adenocarcinoma, occurring in 40 -88% of cancers (Hamelin et al, 1994;Gleeson et al, 1995Gleeson et al, , 1998Soslow et al, 1999) and 30 -66% of Barrett's epithelium with mild or no dysplasia (Hamelin et al, 1994;Neshat et al, 1994). Between 50 and 80% of documented Barrett's p53 mutations are mis-sense (GC-AT base transitions at CpG islands) and 10 -50% are nonsense (Huang et al, 1993;Gleeson et al, 1998).…”

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confidence: 99%

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Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma

et al. 2003

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p53 mutations and loss of heterozygosity have been commonly associated with oesophageal adenocarcinoma. In this investigation, the p53 status of a Welsh population of Barrett's-associated oesophageal adenocarcinomas were fully characterised at the gene sequence, chromosomal, mRNA and protein levels. In total, 31 tumours were examined for p53 gene sequence mutations using RFLP with sequencing, allelic loss of the gene was characterised by FISH, mRNA expression by p53 pathway signalling arrays and protein levels by p53 immunohistochemistry. In all, 9.6% of adenocarcinomas harboured p53 mutations, 24% displayed p53 allelic loss and 83% exhibited p53 protein accumulation. Point mutations and deletions of the gene did not coexist within the same samples. All samples containing p53 mutations also displayed positive immunostaining; however; in the majority of cases, p53 protein accumulation developed in the absence of mutations. The gene expression analysis demonstrated no differences in p53 and mdm-2 transcription levels between the p53 immunonegative and immunopositive samples, indicating other mechanisms underlie the proteins' overexpression. In conclusion, p53 mutations and deletions do not appear to be frequent events in oesophageal adenocarcinomas; however, abnormal accumulation of the protein is present in a vast majority of cases. P53 gene mutations are not the primary cause of protein overexpression -an alternative mechanism is responsible for the positive p53 immunohistochemistry detected.

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Section: Discussioncontrasting

confidence: 56%

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confidence: 99%

Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma

et al. 2003

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“…Mutation of the p53 tumour-suppressor gene has been reported as extremely frequent in BA (Hamelin et al, 1994b;Gleeson et al, 1995) and SCC (Audrezet et al, 1993;Muzeau et al, 1996). In colorectal cancer, it appears that there is an inverse relationship between the presence of p53 gene mutation and the RER+ phenotype (Kim et al, 1994;Cottu et al, 1996).…”

Section: Resultsmentioning

confidence: 99%

Infrequent microsatellite instability in oesophageal cancers

Muzeau

Jf²,

Belghiti³

et al. 1997

Br J Cancer

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Summary Alterations of microsatellites have been found at relatively high frequency in hereditary and sporadic colorectal cancer and gastric and pancreatic cancers and at lower frequency in some other cancers. We determined the frequency of instability at 39 poly-CA microsatellite loci in 20 squamous cell carcinomas and 26 Barrett's adenocarcinomas of the oesophagus. None of the tumours presented instability for a high percentage of the tested loci. Four squamous cell carcinomas and six Barrett's adenocarcinomas showed microsatellite instability at one locus, and three Barrett's adenocarcinomas showed microsatellite instability at two loci. The presence of few loci showing microsatellite instability could be due to an instability background. We conclude that genetic defects in the DNA mismatch repair system do not play an important role in oesophageal cancers.Keywords: microsatellite instability; cancer of the oesophagus; squamous cell carcinoma of the oesophagus; Barrett's adenocarcinoma; DNA mismatch repair system Recently a new class of genetic alterations in human tumours has been described Thibodeau et al, 1993). These appear at microsatellite loci that are short, repeated nucleotide sequences distributed within the normal genome. Alterations of microsatellites consist of the loss or gain of one or more repeat units in tumours compared with matched normal DNA and have been termed microsatellite instability (MI). MI was first described in colorectal cancer, in both hereditary non-polyposis colorectal cancer (HNPCC) and sporadic colorectal cancer cases Thibodeau et al, 1993), as a result of a deficient DNA mismatch repair system (Fishel et al, 1993;Leach et al, 1993;Parsons et al, 1993;Bronner et al, 1994;Papadopoulos et al, 1994). MI has also been observed in a variety of sporadic cancers, such as endometrium, stomach, kidney, ovary and pancreas cancers, belonging to the HNPCC tumour spectrum (Han et al, 1993;Peltomaki et al, 1993;Risinger et al, 1993). In bladder, breast and lung cancers, MI has been reported with variable frequency (Gonzalez-Zulueta et al, 1993;Merlo et al, 1994; Schridar et al, 1994). There are conflicting reports concerning the presence of MI in oesophageal cancers (Meltzer et al, 1994;Keller et al, 1995;Mironov et al, 1995;Nakashima et al, 1995;Gleeson et al, 1996). Cancer of the oesophagus is among the most common and severe malignant neoplasms in the world (Muller et al, 1990;Parkin et al, 1993). There are two main histological types of oesophageal cancer, squamous cell carcinoma (SCC) and Barrett's adenocarcinoma (BA). SCC is more frequent and is associated with alcohol and tobacco consumption in Western countries (Tomatis et al, 1990

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“…62,64 Although most research in Barrett's esophagus has focused on mutations occurring in the mutation cluster region in exons 5-8 of the p53 gene, it is conceivable that mutations in other exons or in related proteins could also affect biological function. Interpretation is further complicated by the lack of data concerning the normal clonal colonization patterns of Barrett's crypts such as have recently been noted in the colon and termed patch size.…”

Section: Development Of Invasive Adenocarcinoma: Generation Of Tumor mentioning

confidence: 99%

Molecular Evolution of the Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus

Jankowski

Wright

Meltzer

et al. 1999

The American Journal of Pathology

365

254

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The incidence of adenocarcinoma of the esophagus has been increasing in developing countries over the last three decades and probably reflects a genuine increase in the incidence of its recognized precursor lesion , Barrett's metaplasia. Despite advances in multimodality therapy , the prognosis for invasive esophageal adenocarcinoma is poor. An improved understanding of the molecular biology of this disease may allow improved diagnosis , therapy , and prognosis. We focus on recent developments in the molecular and cell biology of Barrett's metaplasia , a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally. Early premalignant clones produce biological and genetic heterogeneity as seen by multiple p53 mutations , p16 mutations , aneuploidy , and abnormal methylation resulting in stepwise changes in differentiation , proliferation , and apoptosis , allowing disease progression under selective pressure. Abnormalities in expression of growth factors of the epidermal growth factor family and cell adhesion molecules, especially cadherin/catenin complexes , may occur early in invasion. Exploitation of these molecular events may lead to a more appropriate diagnosis and understanding of these lesions in the future. (Am J Pathol 1999, 154:965-973)

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TP53 gene mutations and p53 protein immunoreactivity in malignant and premalignant Barrett's esophagus

Cited by 150 publications

References 31 publications

Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma

Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma

Infrequent microsatellite instability in oesophageal cancers

Molecular Evolution of the Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus

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