Genomic instability in Ip and human malignancies

Schwab, Manfred; Praml, Christian; Amler, Lukas C.

doi:10.1002/(sici)1098-2264(199608)16:4<211::aid-gcc1>3.0.co;2-0

Cited by 193 publications

(109 citation statements)

References 156 publications

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“…The p73 protein also shares some functional characteristics with p53, including the ability to promote apoptosis when over-expressed in vitro and upregulate p53 responsive genes involved in cell-cycle control such as p21 [53]. Loss of heterozygosity of 1p is common in human neoplasias including neuroblastoma, melanoma, hepatocellular carcinoma, colorectal carcinoma, and breast cancer [54]. We detected p73 over-expression in 30% of patients by immunohistochemical analysis using p73 monoclonal antibody.…”

Section: Expression Of P73 Proteinmentioning

confidence: 86%

Alteration of p73 in acute myelogenous leukemia

et al. 2005

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The frequency of p73 mutation is low in hematologic malignancies as well as solid tumors. In the present study, we scanned for mutations in the exons 4, 5, 6, and 7 of p73, as well as methylation of the CpG island in the untranslated region of exon 1, in 100 de novo AML patients. Four patients showed mutation in exon 5 and one in exon 6, and none of the patients showed mutation in exons 4 and 7. None of the patients showed p73 gene methylation. The expression level of p73 mRNA was also examined in 40 AML samples using reverse transcriptase-polymerase chain reaction. Only six AML patients showed p73 mRNA expression, as analyzed by RT-PCR analysis. However, p73 over-expression in 30% of patients was demonstrated by immunocytochemistry and Western blot analysis. Further, mutation of p73 has been correlated with p73 mRNA and p73 protein status. The results show the presence of over-expressed p73 mRNA and protein in the samples with mutated p73 gene. Thus, it is presumed that mutation of p73 might lead to production of defective p73 protein and p73 mRNA, and this might have a role in the process of leukemogenesis of AML. This report is the first demonstrating the presence of mutations in p73 gene in acute myelogenous leukemia. Am.

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Section: Expression Of P73 Proteinmentioning

confidence: 86%

Alteration of p73 in acute myelogenous leukemia

et al. 2005

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“…Our study further supports a role for RUNX3 in pancreatic cancer. The 1p36 region is believed to harbour tumour suppressor genes, because previous studies identified frequent allelic imbalance at 1p36 in various types of human cancers (Schwab et al, 1996). RIZ1 and p73 genes are located on 1p36, and LOH was detected at each gene locus in pancreatic cancer (Sakurada et al, 2001;Sphyris et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer

et al. 2008

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Alteration in transforming growth factor-b signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P ¼ 0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.

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“…Hot-spots for genomic alteration have been described for various tumors 35,36 and may include genes affecting pathways common to cancer biology such as cell cycle regulation, mechanisms of invasion, and metastasis. For instance, several regions of chromosome 1p, including 1p36 and 1p22, have been implicated in the tumorigenesis of a wide range of malignancies.…”

Section: Discussionmentioning

confidence: 99%