Project description:A survey of the somatic allelic imbalances and copy number alterations in HER2-amplified breast cancer. Genomic profiling of 26 breast tumors with amplification of HER2 using 1M and 2.5M Illumina SNP beadchips. Sample identifiers correspond to GSE21259 where sample annotations may be extracted.
Project description:This SuperSeries is composed of the following subset Series: GSE29016: Relation between smoking history and gene expression profiles in lung adenocarcinomas GSE29065: Landscape of somatic allelic imbalances and copy number alterations in human lung carcinoma Refer to individual Series
Project description:Lung cancer is the worldwide leading cause of death from cancer. This GEO series correspond to one of the BAC aCGH data sets used as validation cohort for the study: Landscape of somatic allelic imbalances and copy number alterations in human lung cancer, Int J Cancer 2013.
Project description:Lung cancer is the worldwide leading cause of death from cancer. This GEO series correspond to one of the BAC aCGH data sets used as validation cohort for the study: Landscape of somatic allelic imbalances and copy number alterations in human lung cancer, Int J Cancer 2012. Genomic profiling of 78 lung carcinomas using 32K BAC aCGH microarrays.
Project description:B cell non-Hodgkin's lymphoma (B-NHL) consists of different pathological entities that are frequently characterized by distinct genetic alterations. However, the knowledge on these genetic lesions in B-NHL is still limited. In order to obtain a more comprehensive view of genetic lesions in B-NHL, we performed genome-wide analysis of copy number (CN) alterations as well as allelic imbalances using Affymetrix SNP arrays with B-NHL cases, including SNP array data were analyzed with CNAG/AsCNAR software, which enabled sensitive detection of CN alterations in allele-specific manner, and thus allelic imbalances, without depending on availability of paired normal controls. Most frequent numerical abnormalities in B-NHL were gains of chromosomes 3 and 18, although gains of chromosome 3 were less prominent in FL. Chromosomal deletions that lead to loss of heterozygosity (LOH) were commonly found in 1p, 6q and 10q. High-grade amplifications and homozygous deletions frequently provide a clue to identify relevant gene targets. In our series, 12 loci of high-grade amplifications and 14 loci of homozygous deletions were identified, and helped to specify the candidate genes. These regions included, FCGR2B amplified in 5 cases of DLBCL, RERE amplified in 2 cases of FL and CDKN2A/CDKN2B deleted in 9 cases of DLBCL.
Project description:High-resolution microarray-based whole genome genotyping (WGG) techniques based on SNP analysis have successfully been applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Problems in data interpretation arise when WGG is applied on tumor tissue specimens, in which normal cell components and tumor subpopulations frequently exist. Such heterogeneity may lead to reduced detection of cancer cell specific genomic alterations. To circumvent problems with sample heterogeneity, we propose using a segmentation strategy derived from DNA copy number analysis for detection of LOH and allelic imbalance. We generated an experimental dilution series of a tumor cell line mixed with its paired normal cell line and simulated data for such dilutions to test the strategy. We also used data sets generated on both Affymetrix and Illumina WGG platforms, including paired tumor-normal samples and tumors previously characterized by FISH. We tested the segmentation strategy against several reported algorithms. We demonstrate high sensitivity and specificity of the segmentation strategy for detecting both minute and gross allelic imbalances originating from DNA copy number gain, loss, and neutral events in tumor specimens. For example, hemizygous copy number loss can be detected in samples containing only 20-25% tumor cells. Furthermore, the strategy can identify cell subpopulation specific events and accurately estimate the fraction of cells affected by an allelic imbalance. Thus, the segmentation strategy extends the usefulness of WGG platforms for investigation of allelic imbalances in heterogeneous tumor genomes.
Project description:We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. Our results indicate that even driver genetic alterations, such as HER2, can be heterogeneously distributed in a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification.