Infrequent alterations of the APC and MCC genes in gastric cancers from British patients

Sud, Richa; Talbot, Ian C.; Delhanty, Jda

doi:10.1038/bjc.1996.497

Cited by 21 publications

(14 citation statements)

References 29 publications

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“…Here, 18% (score) and 36% (matched pair analysis) of our cases showed an LOH at 5q, where the candidate genes APC, MCC and IRF-1 are located. As mutations of the retained allele of APC in Barrett's adenocarcinoma 43 and of MCC in gastric cancer 44 are not very frequent, there may be another target gene on 5q, such as IRF-1, which can induce apoptosis of esophageal adenocarcinoma cells in vitro. 45 However, the least common LOH area (score) in our study was 5q32-5q35.1, harboring Genetic alterations in Barrett's carcinoma T Wiech et al genes such as ECRG2, a candidate of tumor suppressor gene in esophageal squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of genetic alterations in Barrett's adenocarcinoma using single nucleotide polymorphism arrays

Wiech

Nikolopoulos

Weis

et al. 2009

Laboratory Investigation

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We performed genome-wide analysis of copy-number changes and loss of heterozygosity (LOH) in Barrett's esophageal adenocarcinoma by single nucleotide polymorphism (SNP) microarrays to identify associated genomic alterations. DNA from 27 esophageal adenocarcinomas and 14 matching normal tissues was subjected to SNP microarrays. The data were analyzed using dChipSNP software. Copy-number changes occurring in at least 25% of the cases and LOH occurring in at least 19% were regarded as relevant changes. As a validation, fluorescence in situ hybridization (FISH) of 8q24.21 (CMYC) and 8p23.1 (SOX7) was performed. Previously described genomic alterations in esophageal adenocarcinomas could be confirmed by SNP microarrays, such as amplification on 8q (CMYC, confirmed by FISH) and 20q13 or deletion/LOH on 3p (FHIT) and 9p (CDKN2A). Moreover, frequent gains were detected on 2p23.3, 7q11.22, 13q31.1, 14q32.31, 17q23.2 and 20q13.2 harboring several novel candidate genes. The highest copy numbers were seen on 8p23.1, the location of SOX7, which could be demonstrated to be involved in amplification by FISH. A nuclear overexpression of the transcription factor SOX7 could be detected by immunohistochemistry in two amplified tumors. Copy-number losses were seen on 18q21.32 and 20p11.21, harboring interesting candidate genes, such as CDH20 and CST4. Finally, a novel LOH region could be identified on 6p in at least 19% of the cases. In conclusion, SNP microarrays are a valuable tool to detect DNA copynumber changes and LOH at a high resolution. Using this technique, we identified several novel genes and DNA regions associated with esophageal adenocarcinoma. KEYWORDS: Barrett's adenocarcinoma; copy-number changes; esophageal carcinoma; LOH; mapping array; SNP array Genomic alterations, such as amplification, deletion, translocation and loss of heterozygosity (LOH) play an important role in the pathogenesis and progression of cancer due to the activation of oncogenes or inactivation of tumor suppressor genes. Apart from numeric aberrations, such as gene amplification or deletion, which are frequently detected in carcinomas, other genomic changes in carcinogenesis, such as LOH, do not necessarily lead to DNA copy-number gain or loss. Several causes of LOH have been described, including deletion, non-disjunction and reduplication, mitotic recombination and gene conversion. 1 The two-hit model describes a tumor suppressor gene inactivation due to a loss of one allele and mutation of the other allele, resulting in an LOH. 2 Besides detailed investigation of known oncogenes and tumor suppressor genes, screening for novel genomic alterations in different cancers and precursor lesions provides information of molecular mechanisms in carcinogenesis.The incidence of esophageal (Barrett's) adenocarcinoma, mostly arising within the precancerous Barrett's esophagus, with the normal esophageal squamous epithelium changed into intestinal metaplasia, has risen in the past decades in western countries. 3 Screening for chromosomal alterations has bee...

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Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of genetic alterations in Barrett's adenocarcinoma using single nucleotide polymorphism arrays

Wiech

Nikolopoulos

Weis

et al. 2009

Laboratory Investigation

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“…Observations from colorectal and gastric cancers suggest that despite the high frequency of loss of heterozygosity of the MCC gene, mutation of the retained MCC allele is uncommon. 75,76 This suggests that MCC does not function as a tumor suppressor gene in gastrointestinal malignancies. IFNA, interferon-alfa gene; NF1, neurofibromatosis gene; CSF3, colony stimulating factor 3; erbB-2, member of epidermal growth factor receptor family; ITB4, integrin-beta 4; MSH3, DNA mismatch repair gene; Rb, retinoblastoma; VHL, von Hippel Lindau gene; PPAR␥, peroxidase proliferator-activated receptor-␥; MCC, mutated in colorectal cancer; APC, adenomatous polyposis coli; IRF-1, interferon regulatory factor 1; TOC, tylosis esophageal cancer gene; DCC, deleted in colorectal carcinoma; DPC4, deleted in pancreatic carcinoma, locus 4; TP53, p53 tumor suppressor gene; BRCA1, breast cancer gene; WT2, Wilms' tumor suppressor gene; H19, gene involved in genomic imprinting; p57KIP2, a cyclin-dependent kinase inhibitor; HIC1, hypermethylated in cancer; OVCA1/2, ovarian cancer tumor suppressor genes 1 and 2; GH, growth hormone gene; Smad-2, signal transduction molecule involved in TGF-␤ signaling pathway.…”

Section: Chromosome 5qmentioning

confidence: 99%

Molecular Biology of Barrett’s Adenocarcinoma

Wijnhoven

Tilanus²,

Dinjens³

2001

Annals of Surgery

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ObjectiveTo review the current knowledge on the genetic alterations involved in the development and progression of Barrett's esophagus-associated neoplastic lesions. Summary Background DataBarrett's esophagus (BE) is a premalignant condition in which the normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. BE predisposes patients to the development of esophageal adenocarcinoma. Endoscopic surveillance can detect esophageal adenocarcinomas when they are early and curable, but most of the adenocarcinomas are detected at an advanced stage. Despite advances in multimodal therapy, the prognosis for invasive esophageal adenocarcinoma is poor. A better understanding of the molecular evolution of the Barrett's metaplasia to dysplasia to adenocarcinoma sequence may allow improved diagnosis, therapy, and prognosis. MethodsThe authors reviewed data from the published literature to address what is known about the molecular changes thought to be important in the pathogenesis of BE-associated neoplastic lesions. ResultsThe progression of Barrett's metaplasia to adenocarcinoma is associated with several changes in gene structure, gene expression, and protein structure. Some of the molecular alterations already showed promise as markers for early cancer detection or prognostication. Among these, alterations in the p53 and p16 genes and cell cycle abnormalities or aneuploidy appear to be the most important and well-characterized molecular changes. However, the exact sequence of events is not known, and probably multiple molecular pathways interact and are involved in the progression of BE to adenocarcinoma. ConclusionsFurther research into the molecular biology of BE-associated adenocarcinoma will enhance our understanding of the genetic events critical for the initiation and progression of Barrett's adenocarcinoma, leading to more effective surveillance and treatment.Since 1970, the incidence of adenocarcinomas of the esophagus has increased in many countries at a rate that exceeds that of any other malignancy.

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“…For example, Sasaki et al [30] found no β-catenin mutation in gastric cancer tissues, whereas they observed nuclear β-catenin staining in 23% of the same cancer tissues. Also, truncation mutations of APC gene were rarely detected in gastric cancer tissues [31]. AXIN1 mutation is observed frequently in hepatocellular carcinomas [9], but it has not been reported in gastric cancers.…”

Section: Discussionmentioning

confidence: 99%

Frameshift mutations of Wnt pathway genes AXIN2 and TCF7L2 in gastric carcinomas with high microsatellite instability

Kim

Ahn

et al. 2009

Human Pathology

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Infrequent alterations of the APC and MCC genes in gastric cancers from British patients

Cited by 21 publications

References 29 publications

Genome-wide analysis of genetic alterations in Barrett's adenocarcinoma using single nucleotide polymorphism arrays

Genome-wide analysis of genetic alterations in Barrett's adenocarcinoma using single nucleotide polymorphism arrays

Molecular Biology of Barrett’s Adenocarcinoma

Frameshift mutations of Wnt pathway genes AXIN2 and TCF7L2 in gastric carcinomas with high microsatellite instability

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