Esophageal squamous cell carcinomas with DNA replication errors (RER + ) are associated with p16/pRb loss and wild-type p53

Mathew, Robin; Arora, Sonia; Mathur, Meera; Tk, Chattopadhyay; Ralhan, Ranju

doi:10.1007/s004320100249

Cited by 13 publications

(9 citation statements)

References 25 publications

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“…To the best of our knowledge, there is no published data on LOH or MSI at the RBL2/p130 gene locus in retinoblastoma although LOH in the 16q12 region was demonstrated in other neoplasms like multiple myeloma, hepatocellular carcinoma and esophageal squamous cell carcinoma. [12][13][14][15] Besides these, gross allelic loss detected by comparative genomic hybridization and other cytogenetics studies were shown at this chromosomal region in neuroblastoma, and hepatocellular, prostate and breast carcinomas. 16,17 Our results show that 57.9% of the informative retinoblastoma tumors have allelic loss within the RBL2/130 gene.…”

Section: Discussionmentioning

confidence: 85%

High incidence of allelic loss at 16q12.2 region spanning RB2/p130 gene in retinoblastoma

Kadam¹,

Jada²,

Quah³

et al. 2009

Cancer Biology & Therapy

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Retinoblastoma (Rb) is the most common intra-ocular tumor that manifests in early childhood. It is initiated by the inactivation of RB1/p105 gene, a prototype tumor suppressor gene. However, observed recurrent chromosomal aberrations accompanying RB1/p105 mutations suggest the involvement of additional mutational events. Chromosome 16q is one of the loci with recurrent losses which are likely to contain tumor suppressor genes. In this study, allelic loss was demonstrated at a second locus for retinoblastoma, RBL2/p130 on 16q12.2. Using intragenic single nucleotide polymorphisms (SNPs) (rs1074182 and rs10748) and flanking extragenic microsatellite markers (D16S411 and D16S408), 40 retinoblastoma tumor samples were analyzed. Loss of heterozygosity (LOH) of these markers was found in 11 (57.9%) out of 19 informative tumors at the RBL2/p130 gene locus and while a total of 15 (78.9%) tumors showed LOH in at least one marker. Deletions extending more than 13 cM across the pericentromeric region of 16q12.1-q13 were inferred from four tumors. Microsatellite instability was observed in two other tumors at the flanking markers. No mutations were found in RBL2/p130 exons 19-22 coding for the protein domain critical for biological activity. This is the first evidence of LOH within RBL2/p130 gene in retinoblastoma. The high frequency of allelic loss provides further evidence on the implication of this gene in retinoblastoma development and/or progression.

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Section: Discussionmentioning

confidence: 85%

High incidence of allelic loss at 16q12.2 region spanning RB2/p130 gene in retinoblastoma

Kadam¹,

Jada²,

Quah³

et al. 2009

Cancer Biology & Therapy

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“…That study was carried out at seven microsatellite markers in the 2p, 3p, and 16q loci in a cohort of patients from the Indian population. 24 Thus, there are large discrepancies in the findings from these studies, probably as a result of the different technologies used in the various studies, the number of cases and microsatellite markers investigated, and also the specific microsatellite markers used in the studies. Another important factor that cannot be ignored is the fact that these findings are a true reflection of the population genetics of the population group being investigated.…”

Section: Discussionmentioning

confidence: 98%

Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa

Naidoo

Ramburan²,

Reddi³

et al. 2005

J Clin Pathol

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Aims: To investigate the incidence of genetic aberrations in the DNA repair genes in a cohort of oesophageal cancers. Methods: One hundred oesophagectomy samples of squamous cell carcinoma were studied. Normal and tumour DNA were isolated using a standard phenol/chloroform extraction procedure. Six recommended microsatellite loci with high informativity were analysed. The following markers were used: D2S123 (2p), D3S659 (3p), D3S1255 (3p), Bat 25 (4q), Bat 26 (2p), and Bat 40 (1p). The results were analysed using software attached to an automated DNA sequencer. The molecular data were then correlated with clinicopathological parameters. Results: The incidence of microsatellite instability and loss of heterozygosity was very low. There was no significant correlation between the clinicopathological and molecular data. However, D2S123 genetic abnormalities were seen more frequently in both moderately and well differentiated tumours than in poorly differentiated tumours (p = 0.033). Follow up data were available for only 67 of the 100 patients. Fifty patients were alive and 17 patients had died. Conclusion: Low frequencies of genetic aberrations in these mismatch repair loci are found in squamous carcinomas of the oesophagus from a high incidence area in South Africa. O esophageal cancer is the most common malignancy in black South African men, accounting for 14.3% of all cancers in South Africa.1 Over and above the various environmental factors that impact on the development of cancer in general, great advances have been made during the past decade in our understanding of the molecular mechanisms that occur in the transition from normal mucosa, through dysplasia, and finally to carcinoma.2-4 Several studies have revealed that an accumulation of genetic alterations gives rise to cancer. Furthermore, microsatellite instability (MSI) and loss of heterozygosity (LOH) at highly informative genetic loci at which tumour suppressor genes and oncogenes are located are thought to play a role in carcinogenesis. [5][6][7][8][9][10] Genes investigated in recent studies include p53, Rb, DCC, APC, and MCC. 11 We recently showed that the occurrence of MSI in South African squamous carcinomas of the oesophagus was similar to other high incidence areas. ''The mismatch repair genes play an important role in ensuring that errors occurring during DNA synthesis are corrected'' However, very little is known about the status of the mismatch repair genes and their impact on oesophageal cancer. The mismatch repair genes play an important role in ensuring that errors occurring during DNA synthesis are corrected. These genes were initially identified in bacterial systems and mutations in DNA mismatch repair genes have been associated with hereditary non-polyposis colorectal cancer.12-14 Five human DNA mismatch repair genes have been identified, which when mutated cause susceptibility to both sporadic and hereditary non-polyposis colorectal cancer. Mutational inactivation of both copies of a mismatch repair gene results in a profound repair de...

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“…MLH1 promoter hypermethylation has been suggested to be the main cause of MLH1 silencing, leading to microsatellite instability (MSI). In ESCC, MSI is observed in 8-59 % of tumors [58][59][60][61][62][63][64][65]. Loss of the MLH1 protein was found in 72 % of ESCC tumors, concordant with MLH1 promoter hypermethylation [66].…”

Section: Alterations In Dna Methylation In Esccmentioning

confidence: 98%

A review of the alterations in DNA methylation in esophageal squamous cell carcinoma

2013

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Epigenetic changes such as DNA methylation, histone modification, and loss of genome imprinting play a crucial role in esophageal squamous cell carcinogenesis, along with genomic and genetic alterations. DNA methylation is a fundamental epigenetic process that modulates gene expression. Cancer cells exhibit two types of alterations of DNA methylation: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. In several types of human cancers, the methods of detecting an aberrant methylation status have been applied to clinical fields to stratify high-risk groups, detect early cancer, and predict clinical outcomes. Importantly, epigenetic changes, including alterations in DNA methylation, are reversible and can thus be targets for cancer therapy or chemoprevention. Therefore, a better understanding of the DNA methylation in esophageal squamous cell carcinoma (ESCC) is important for optimizing cancer therapy and chemoprevention. We herein summarize the current knowledge regarding alterations in DNA methylation and the clinical implications in ESCC.

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Esophageal squamous cell carcinomas with DNA replication errors (RER + ) are associated with p16/pRb loss and wild-type p53

Cited by 13 publications

References 25 publications

High incidence of allelic loss at 16q12.2 region spanning RB2/p130 gene in retinoblastoma

High incidence of allelic loss at 16q12.2 region spanning RB2/p130 gene in retinoblastoma

Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa

A review of the alterations in DNA methylation in esophageal squamous cell carcinoma

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