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PLoS One. 2010 Oct 29;5(10):e13752. doi: 10.1371/journal.pone.0013752.

Mapping of genetic abnormalities of primary tumours from metastatic CRC by high-resolution SNP arrays.

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1
Servicio General de Citometría, Departamento de Medicina and Centro de Investigación del Cáncer (IBMCC-CSIC/USAL), Universidad de Salamanca, Salamanca, Spain.

Abstract

BACKGROUND:

For years, the genetics of metastatic colorectal cancer (CRC) have been studied using a variety of techniques. However, most of the approaches employed so far have a relatively limited resolution which hampers detailed characterization of the common recurrent chromosomal breakpoints as well as the identification of small regions carrying genetic changes and the genes involved in them.

METHODOLOGY/PRINCIPAL FINDINGS:

Here we applied 500K SNP arrays to map the most common chromosomal lesions present at diagnosis in a series of 23 primary tumours from sporadic CRC patients who had developed liver metastasis. Overall our results confirm that the genetic profile of metastatic CRC is defined by imbalanced gains of chromosomes 7, 8q, 11q, 13q, 20q and X together with losses of the 1p, 8p, 17p and 18q chromosome regions. In addition, SNP-array studies allowed the identification of small (<1.3 Mb) and extensive/large (>1.5 Mb) altered DNA sequences, many of which contain cancer genes known to be involved in CRC and the metastatic process. Detailed characterization of the breakpoint regions for the altered chromosomes showed four recurrent breakpoints at chromosomes 1p12, 8p12, 17p11.2 and 20p12.1; interestingly, the most frequently observed recurrent chromosomal breakpoint was localized at 17p11.2 and systematically targeted the FAM27L gene, whose role in CRC deserves further investigations.

CONCLUSIONS/SIGNIFICANCE:

In summary, in the present study we provide a detailed map of the genetic abnormalities of primary tumours from metastatic CRC patients, which confirm and extend on previous observations as regards the identification of genes potentially involved in development of CRC and the metastatic process.

PMID:
21060790
PMCID:
PMC2966422
DOI:
10.1371/journal.pone.0013752
[Indexed for MEDLINE]
Free PMC Article
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