Chromosomal Alterations during Lymphatic and Liver Metastasis Formation of Colorectal Cancer

Knösel, Thomas; Schlüns, Karsten; Stein, Ulf; Schwabe, Holger; Schlag, Peter M.; Dietel, Manfred; Petersen, Iver

doi:10.1016/s1476-5586(04)80050-2

Cited by 75 publications

(50 citation statements)

References 26 publications

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“…The human miR-320a gene is located at chromosome 8p21.3. The region of chromosome 8p21-22 has been identified as a liver metastatic susceptibility locus whose disruption increases metastatic potential (44). Chromosome 8p is also frequently lost in late stage and metastatic CRC (45,46).…”

Section: Discussionmentioning

confidence: 99%

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Zhang

Liu

et al. 2011

Oncol Rep

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Abstract. MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that various miRNAs function as oncogenes or tumor suppressors in colorectal cancer (CRC), the role of miRNAs in mediating liver metastasis remains unexplored. The expression profile of miRNAs in liver metastasis and primary CRC tissues was analyzed by miRNA microarrays and verified by real-time polymerase chain reaction (PCR). In 62 CRC patients, the expression levels of miR-320a were determined by real-time PCR, and the effects on migration and invasion of miR-320a were determined using a transwell assay. miR-320a target genes were confirmed by luciferase assay, real-time PCR and Western blot analysis. A set of miRNAs was found to be dysregulated in the liver metastasis tissues compared to matched primary CRC tissues, and the expression levels of miR-320a were significantly decreased in the liver metastasis tissues examined. miR-320a was correlated with tumor progression in CRC. miR-320a was downregulated in liver metastatic colon cancer cells and inhibited liver metastatic colon cancer cell migration and invasion. miR-320a directly binds to the 3'UTR of neuropilin 1 (NRP-1), a protein that functions as a co-receptor of vascular epithelial growth factor. miR-320a downregulated the expression of NRP-1 at both the mRNA and protein levels. These data demonstrated that miR-320a may be useful for identifying CRC patients that are at an elevated risk for developing liver metastasis. Our findings suggest that miR-320a may be a novel therapeutic candidate for the treatment of colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Zhang

Liu

et al. 2011

Oncol Rep

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“…Researchers have developed genetic models depicting the accumulation of DNA CN changes in disease progression (Knosel et al, 2004;Diep et al, 2006). A well-defined study that examined genomic changes in various stages of CRC has also shown that genomic changes increase significantly from 4 (Dukes' A) to 16% (Dukes' D) of the entire genome (Lagerstedt et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Genome-wide analyses of chromosomal CN abnormalities (CNAs) have provided insight on CRC carcinogenesis, including defining the genomic events that occur during various stages, although the results are inconsistent (Aragane et al, 2001;Choi et al, 2002;He et al, 2003;Knosel et al, 2004;Diep et al, 2006;Sheffer et al, 2009;Lagerstedt et al, 2010;Poulogiannis et al, 2010;Lin et al, 2011). However, reports on the occurrence of copy-neutral LOH have been scant.…”

Section: Introductionmentioning

confidence: 99%

Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients

Yam

Hoh²,

Othman³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Colorectal cancer is one of the most common cancers in many countries, including Malaysia. The accumulation of genomic alterations is an important feature of colorectal carcinogenesis. A better understanding of the molecular events underlying the stages of colorectal carcinogenesis might be helpful in the detection and management of the disease. We used a commercially available singlenucleotide polymorphism genotyping array to detect both copy number abnormalities (CNAs) and copy-neutral loss of heterozygosity (LOH) in sporadic colorectal carcinomas. Matched tumor and normal tissues of 13 colorectal carcinomas (Dukes' stages A-D) were analyzed using a 250K single nucleotide polymorphism array. An additional assay was performed to determine the microsatellite instability status by using the National Cancer Institute-recommended BAT-26 panel. In general, copy number gain (92.3%) was most common, followed by copy number loss (53.8%) and copy-neutral LOH (46.2%). Frequent CNAs of gains and losses were observed on chromosomes 7p, 8, 13q, 17p, 18q, and 20q, and copy-neutral LOH was observed on chromosomes 2, 6, 12, 13q, 14q, 17, 20p, 19q, and 22q. Even though genomic alterations are associated with colorectal cancer progression, our results showed that DNA CNAs and copy-neutral LOH do not reflect disease progression in at least 50% tumors. Copy-neutral LOH was observed in both early and advanced tumors, which favors the involvement of these genomic alterations in the early stages of tumor development.

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“…The term aneusomy is used for a specific, aneuploid chromosome. Specific aneuploidies have even been linked with specific stages of carcinogenesis and with specific phenotypes of cancers such as: (1) Distinct stages of neoplastic transformation in human [62,89,[95][96][97][98][99] and in animal carcinogenesis [84]; (2) invasiveness [97,98,100]; (3) metastasis [101][102][103][104][105][106]; (4) drug-resistance [53,69,107]; (5) transplantability to foreign hosts [108]; (6) distinct cellular morphologies [109]; (7) abnormal metabolism [62,110], and (8) cancer-specific receptors for viruses [62,109].…”

Section: Cancer-specific Aneuploidiesmentioning

confidence: 99%

Aneuploidy and Cancer: From Correlation to Causation

Duesberg

Fabarius³

et al. 2006

Infection and Inflammation: Impacts on Oncogenesis

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Conventional genetic theories have failed to explain why cancer (1) is not found in newborns and thus not heritable; (2) develops only years to decades after 'initiation' by carcinogens; (3) is caused by non-mutagenic carcinogens; (4) is chromosomally and phenotypically 'unstable'; (5) carries cancer-specific aneuploidies; (6) evolves polygenic phenotypes; (7) nonselective phenotypes such as multidrug resistance, metastasis or affinity for non-native sites and 'immortality' that is not necessary for tumorigenesis; (8) contains no carcinogenic mutations. We propose instead that cancer is a chromosomal disease: Accordingly, carcinogens initiate chromosomal evolutions via unspecific aneuploidies. By unbalancing thousands of genes aneuploidy corrupts teams of proteins that segregate, synthesize and repair chromosomes. Aneuploidy is thus a steady source of karyotypic-phenotypic variations from which, in classical Darwinian terms, selection of cancer-specific aneuploidies encourages the evolution and subsequent malignant 'progressions' of cancer cells. The rates of these variations are proportional to the degrees of aneuploidy, and can exceed conventional mutation by 4-7 orders of magnitude. This makes cancer cells new cell 'species' with distinct, but unstable karyotypes, rather than mutant cells. The cancer-specific aneuploidies generate complex, malignant phenotypes, through the abnormal dosages of the thousands of genes, just as trisomy 21 generates Down syndrome. Thus cancer is a chromosomal rather than a genetic disease. The chromosomal theory explains (1) nonheritability of cancer, because aneuploidy is not heritable; (2) long 'neoplastic latencies' by the low probability of evolving competitive new species; (3) nonselective phenotypes via genes hitchhiking on selective chromosomes, and (4) 'immortality', because chromosomal variations neutralize negative mutations and adapt to inhibitory conditions much faster than conventional mutation. Based on this article a similar one, entitled 'The chromosomal basis of cancer', has since been published by us in Cellular Oncology 2005;27:293-318. Copyright © 2006 S. Karger AG, Basel Despite over 100 years of cancer research, the cause of cancer is still a matter of debate . We propose here that the problem of cancer is still

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Chromosomal Alterations during Lymphatic and Liver Metastasis Formation of Colorectal Cancer

Cited by 75 publications

References 26 publications

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

microRNA-320a inhibits tumor invasion by targeting neuropilinï¿½1 and is associated with liver metastasis in colorectal cancer

Somatic copy-neutral loss of heterozygosity and copy number abnormalities in Malaysian sporadic colorectal carcinoma patients

Aneuploidy and Cancer: From Correlation to Causation

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