Comparison of losses of heterozygosity and replication errors in primary colorectal carcinomas and corresponding liver metastases

Bläker, Hendrik; Graf, Matthias M.; Rieker, Ralf J.; Otto, Herwart F.

doi:10.1002/(sici)1096-9896(199907)188:3<258::aid-path350>3.0.co;2-9

Cited by 39 publications

(24 citation statements)

References 26 publications

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“…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). Given this, it is likely that a reduction in miR-320a expression may also be associated with clinicopathological parameters in primary CRC.…”

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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“…Although several studies have suggested that additional abnormalities can be observed in metastases when compared to primary tumor, 16,17 there is currently a lack of data concerning intermetastatic and intrametastatic variability regarding genetic alterations and chemosensitivity. The aim of our study was to assess intrametastatic and intermetastatic heterogeneity within colorectal liver metastases.…”

mentioning

confidence: 99%

Evidence of heterogeneity within colorectal liver metastases for allelic losses, mRNA level expression and in vitro response to chemotherapeutic agents

Goasguen

Chaisemartin

Brouquet

et al. 2010

Intl Journal of Cancer

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A goal of oncology is to predict chemosensitivity of tumors. This approach assumes that in a patient all tumor deposits are homogeneous. We have tested the heterogeneity between several samples of the same liver metastasis (LM; intrametastatic heterogeneity) or between multiple LM (intermetastatic heterogeneity) from colorectal cancer in a single patient. In 16 untreated patients, several fragments of LM and nontumorous liver were collected. Heterogeneity to anticancer drug treatment was assessed in vitro on primary tissue cultures on poly-HEMA-coated surface with or without the topoisomerase-I inhibitor metabolite SN-38. Heterogeneity of response to SN-38 was observed in 55% of cases from one fragment to another in the same LM and in 64% of cases from one LM to another in the same patient. Allelic losses were characterized on 5q, 8p, 17p, 18q, 22q using 29 microsatellites markers. Seven patients (58%) had a perfect homogeneity for allelic losses in their LM whereas 3 (21%) had intrametastatic and 2 (18%) had intermetastatic heterogeneity. The analysis of gene expression was carried out by real time RT-PCR quantification using specific probes for TS, TOPO1, ERCC1, and CES2. Level expression of genes tested appeared heterogeneous with average variations of 57(623)%, 52(618)%, 53(618)%, 56(616)% for TS, TOPO1, ERCC1, and CES2 respectively for intermetastatic variability and 47(626)%, 36(614)%, 38(619)%, and 56(629)%, respectively for intrametastatic variability. Our results demonstrate intermetastatic and intrametastatic heterogeneity suggesting that pretherapeutic analysis of a single tumor biopsy is likely to lead to a misinterpretation of sensitivity to anticancer treatment.Colorectal carcinoma is one of the most prevalent cancer in western countries.1,2 Nearly 50% of patients suffering from colorectal cancer develop distant metastases at some point during the course of their disease, which represents the main cause of cancer related death. In case of liver metastases, treatment is based upon surgical resection but only 10-20% of metastases are amenable to resection.3 Patients with multiple liver metastases receive systemic chemotherapy.The increasing number of active cytotoxic drugs and targeted therapies has placed clinicians in front of a broad spectrum of therapeutic options. [4][5][6][7][8] Predictive factors for the response to chemotherapy are currently extensively studied in order to identify markers of chemosensitivity or chemoresistance which could guide oncologists for the choice of the most effective drug for a given patient. [9][10][11][12][13][14][15] To date, most of these studies aiming to determine a molecular signature of the tumor are conducted from DNA or RNA extracted from a single tumor biopsy either on primary tumor or metastases.Validity of such an approach predicting chemosensitivity is based on the clonality of molecular alterations within the tumor and metastases, in other word considering that all part of the tumor and all tumor deposits (i.e., primary and metastases) have the same m...

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“…12 Interestingly, LOH at 3p25 and 3p23 has been associated with lymph node metastases in squamous-cell carcinoma of the esophagus and with colorectal cancers and poor survival in patients with colorectal carcinoma, respectively. [13][14][15] A second candidate gene on 3p25 is PPAR␥, a member of the nuclear receptor superfamily. This gene is involved in adipocyte differentiation, cholesterol homeostasis, lipogenesis, thermogenesis and glucose homeostasis.…”

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confidence: 99%

Molecular genetic analysis of the von Hippel-Lindau and human peroxisome proliferator-activated receptor ? tumor-suppressor genes in adenocarcinomas of the gastroesophageal junction

et al. 2001

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Comparison of losses of heterozygosity and replication errors in primary colorectal carcinomas and corresponding liver metastases

Cited by 39 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

Evidence of heterogeneity within colorectal liver metastases for allelic losses, mRNA level expression and in vitro response to chemotherapeutic agents

Molecular genetic analysis of the von Hippel-Lindau and human peroxisome proliferator-activated receptor ? tumor-suppressor genes in adenocarcinomas of the gastroesophageal junction

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