Allele-specific disparity in breast cancer
<p>Abstract</p> <p>Background</p> <p>In a cancer cell the number of copies of a locus may vary due to amplification and deletion and these variations are denoted as copy number alterations (CNAs). We focus on the disparity of CNAs in tumour samples, which were compared...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-12-01
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| Series: | BMC Medical Genomics |
| Online Access: | http://www.biomedcentral.com/1755-8794/4/85 |
| _version_ | 1818556999932051456 |
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| author | Kaveh Fatemeh Edvardsen Hege Børresen-Dale Anne-Lise N Kristensen Vessela Solvang Hiroko K |
| author_facet | Kaveh Fatemeh Edvardsen Hege Børresen-Dale Anne-Lise N Kristensen Vessela Solvang Hiroko K |
| author_sort | Kaveh Fatemeh |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>In a cancer cell the number of copies of a locus may vary due to amplification and deletion and these variations are denoted as copy number alterations (CNAs). We focus on the disparity of CNAs in tumour samples, which were compared to those in blood in order to identify the directional loss of heterozygosity.</p> <p>Methods</p> <p>We propose a numerical algorithm and apply it to data from the Illumina 109K-SNP array on 112 samples from breast cancer patients. B-allele frequency (BAF) and log R ratio (LRR) of Illumina were used to estimate Euclidian distances. For each locus, we compared genotypes in blood and tumour for subset of samples being heterozygous in blood. We identified loci showing preferential disparity from heterozygous toward either the A/B-allele homozygous (allelic disparity). The chi-squared and Cochran-Armitage trend tests were used to examine whether there is an association between high levels of disparity in single nucleotide polymorphisms (SNPs) and molecular, clinical and tumour-related parameters. To identify pathways and network functions over-represented within the resulting gene sets, we used Ingenuity Pathway Analysis (IPA).</p> <p>Results</p> <p>To identify loci with a high level of disparity, we selected SNPs 1) with a substantial degree of disparity and 2) with substantial frequency (at least 50% of the samples heterozygous for the respective locus). We report the overall difference in disparity in high-grade tumours compared to low-grade tumours (p-value < 0.001) and significant associations between disparity in multiple single loci and clinical parameters. The most significantly associated network functions within the genes represented in the loci of disparity were identified, including lipid metabolism, small-molecule biochemistry, and nervous system development and function. No evidence for over-representation of directional disparity in a list of stem cell genes was obtained, however genes appeared to be more often altered by deletion than by amplification.</p> <p>Conclusions</p> <p>Our data suggest that directional loss and amplification exist in breast cancer. These are highly associated with grade, which may indicate that they are enforced with increasing number of cell divisions. Whether there is selective pressure for some loci to be preferentially amplified or deleted remains to be confirmed.</p> |
| first_indexed | 2024-12-13T23:54:25Z |
| format | Article |
| id | doaj.art-cbf687286d8443c0bac5544af1a4fc48 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-13T23:54:25Z |
| publishDate | 2011-12-01 |
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| series | BMC Medical Genomics |
| spelling | doaj.art-cbf687286d8443c0bac5544af1a4fc482022-12-21T23:26:39ZengBMCBMC Medical Genomics1755-87942011-12-014185doi:10.1186/1755-8794-4-85Allele-specific disparity in breast cancerKaveh FatemehEdvardsen HegeBørresen-Dale Anne-LiseN Kristensen VesselaSolvang Hiroko K<p>Abstract</p> <p>Background</p> <p>In a cancer cell the number of copies of a locus may vary due to amplification and deletion and these variations are denoted as copy number alterations (CNAs). We focus on the disparity of CNAs in tumour samples, which were compared to those in blood in order to identify the directional loss of heterozygosity.</p> <p>Methods</p> <p>We propose a numerical algorithm and apply it to data from the Illumina 109K-SNP array on 112 samples from breast cancer patients. B-allele frequency (BAF) and log R ratio (LRR) of Illumina were used to estimate Euclidian distances. For each locus, we compared genotypes in blood and tumour for subset of samples being heterozygous in blood. We identified loci showing preferential disparity from heterozygous toward either the A/B-allele homozygous (allelic disparity). The chi-squared and Cochran-Armitage trend tests were used to examine whether there is an association between high levels of disparity in single nucleotide polymorphisms (SNPs) and molecular, clinical and tumour-related parameters. To identify pathways and network functions over-represented within the resulting gene sets, we used Ingenuity Pathway Analysis (IPA).</p> <p>Results</p> <p>To identify loci with a high level of disparity, we selected SNPs 1) with a substantial degree of disparity and 2) with substantial frequency (at least 50% of the samples heterozygous for the respective locus). We report the overall difference in disparity in high-grade tumours compared to low-grade tumours (p-value < 0.001) and significant associations between disparity in multiple single loci and clinical parameters. The most significantly associated network functions within the genes represented in the loci of disparity were identified, including lipid metabolism, small-molecule biochemistry, and nervous system development and function. No evidence for over-representation of directional disparity in a list of stem cell genes was obtained, however genes appeared to be more often altered by deletion than by amplification.</p> <p>Conclusions</p> <p>Our data suggest that directional loss and amplification exist in breast cancer. These are highly associated with grade, which may indicate that they are enforced with increasing number of cell divisions. Whether there is selective pressure for some loci to be preferentially amplified or deleted remains to be confirmed.</p>http://www.biomedcentral.com/1755-8794/4/85 |
| spellingShingle | Kaveh Fatemeh Edvardsen Hege Børresen-Dale Anne-Lise N Kristensen Vessela Solvang Hiroko K Allele-specific disparity in breast cancer BMC Medical Genomics |
| title | Allele-specific disparity in breast cancer |
| title_full | Allele-specific disparity in breast cancer |
| title_fullStr | Allele-specific disparity in breast cancer |
| title_full_unstemmed | Allele-specific disparity in breast cancer |
| title_short | Allele-specific disparity in breast cancer |
| title_sort | allele specific disparity in breast cancer |
| url | http://www.biomedcentral.com/1755-8794/4/85 |
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