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• W2592685211 abstract "Abstract Unbiased analysis of CLL genomes using intermediate resolution SNP arrays has identified subtypes of del13q14, del17p and del11q as well as high genomic complexity CLL. Additional information on genomic aberrations and polymorphic copy number variants (CNVs) in CLL may be obtained through application of the latest generation ultra-high-density SNP array technology to CLL genome analysis. We have analyzed 50 paired DNA samples (sorted CD19+ cells versus sorted CD3+ cells) from CLL patients with del13q14 type I and del17p on the Affymetrix SNP 6.0 array platform that were previously analyzed on Affy 50K arrays. We have catalogued all somatically acquired lesions as well as all CNVs. In support of data analysis we have refined the software tools PLUT, LOH tool version 2 and dChipSNP. Results: In this cohort of 50 CLL cases in which we had previously identified a total of 98 subchromosomal losses and gains using the 50K SNP array platform, we have now identified 141 such lesions using the SNP 6.0 arrays. Of these CLL cases, 68% had identical lesion calls, 30% of cases displayed more lesions on the 6.0 arrays than on the 50K arrays and only one case had one lesion not identified using the SNP 6.0 array platform. Thus SNP 6.0 arrays allowed for significantly improved short lesion detection, detection of CNVs and improved measurements of genomic complexity in CLL. The breaks of del13q14 type I and del17p lesions were mapped with unprecedented resolution and in some cases have been localized to genomic regions less than 1 kb in length, thus allowing for PCR-based cloning of breaks. CNVs were identified throughout the genome, and were found in combination with monoallelic, somatically acquired genomic lesions (del17p, del13q14 and others) spanning such CNVs, resulting in patchy biallelic (homozogous) genomic losses within these lesions. Such a mechanism of biallelic gene loss (CNV plus paired, somatically acquired subchromosomal gene loss), occurs in otherwise monoallelic deletions and may contribute to the biology of monoallelic lesions in many cancers. As one example, CNVs were identified in CD3+ DNA from CLL patients that are located at approximately 49.448–49.508 Mb physical position on chromosome 13 that converted to homozygous loss in patients with monoallelic del13q14. These CNVs encompassed parts of DLEU2, TRIM13 and KCNRG but did not include the del13q14 resident miR cluster (miR15a/16-1). Such CNVs within del13q14 may have a role in the biology of CLL as they may result in gene expression changes that mimic somatically acquired del13q14 lesions." @default.
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• W2592685211 date "2008-11-16" @default.
• W2592685211 modified "2023-09-30" @default.
• W2592685211 title "Comparative Genomic Analysis of CLL Genomes Using Affymetrix 50K SNP Versus SNP 6.0 Arrays" @default.
• W2592685211 doi "https://doi.org/10.1182/blood.v112.11.3108.3108" @default.
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