Two forms of genetic instability have been observed in colorectal cancer (CRC): chromosomal instability, that is present in 85% cases and is characterized by structural and numerical chromosomal abnormalities (aneuploidy); and microsatellite instability (MSI), characterized by a defi ciency of the mismatch repair system and associated to a normal or quasi-normal karyotype. Recent advances in molecular cytogenetics techniques are likely to introduce a revolution in the fi eld. In the present study we analysed a series of 57 CRC samples and their related normal mucosae by high resolution genomic arrays (Aff ymetrix SNP 6.0 arrays) and set up a series of bioinformatics tools that allow the generation of a rapid report on broad (>25% of a chromosomal arm) and small somatic copy number abnormalities (CNAs), somatic homozygous deletions, focal high level amplifi cations, and regions of loss of heterozygosity (LOH). MSI tumors represented 14% of our CRC series and showed a median values of somatic broad CNAs of 3 (range 1-6), while microsatellite stable (MSS) tumors showed a median value of 12 (range 0-24). Therefore all MSI tumors were below a threshold of 6 CNAs, while 16.2 % of MSS were below this threshold, representing a group of microsatellite and chromosomal stable tumors. No correlation was observed between the number of tumor associated CNAs and the number of somatic copy neutral- LOH regions, suggesting that diff erent mechanisms underlie such chromosomal abnormalities. Analysis of recurrent CNAs identifi ed somatic homozygous deletions that cannot be ascribed to regions of inherent fragility

Recurrent copy number abnormalities and copy neutral-loss of heterozygosity in colorectal cancer identified by high-density SNP array.

Luca T;CASTORINA, Sergio;
2011-01-01

Abstract

Two forms of genetic instability have been observed in colorectal cancer (CRC): chromosomal instability, that is present in 85% cases and is characterized by structural and numerical chromosomal abnormalities (aneuploidy); and microsatellite instability (MSI), characterized by a defi ciency of the mismatch repair system and associated to a normal or quasi-normal karyotype. Recent advances in molecular cytogenetics techniques are likely to introduce a revolution in the fi eld. In the present study we analysed a series of 57 CRC samples and their related normal mucosae by high resolution genomic arrays (Aff ymetrix SNP 6.0 arrays) and set up a series of bioinformatics tools that allow the generation of a rapid report on broad (>25% of a chromosomal arm) and small somatic copy number abnormalities (CNAs), somatic homozygous deletions, focal high level amplifi cations, and regions of loss of heterozygosity (LOH). MSI tumors represented 14% of our CRC series and showed a median values of somatic broad CNAs of 3 (range 1-6), while microsatellite stable (MSS) tumors showed a median value of 12 (range 0-24). Therefore all MSI tumors were below a threshold of 6 CNAs, while 16.2 % of MSS were below this threshold, representing a group of microsatellite and chromosomal stable tumors. No correlation was observed between the number of tumor associated CNAs and the number of somatic copy neutral- LOH regions, suggesting that diff erent mechanisms underlie such chromosomal abnormalities. Analysis of recurrent CNAs identifi ed somatic homozygous deletions that cannot be ascribed to regions of inherent fragility
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/77937
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