Project description:Profiling of DNA copy number alterations by array CGH in 100 sequential samples from 44 patients diagnosed with follicular lymphoma using a inhouse 1 Mb BAC/PAC array CGH
Project description:Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF. Keywords: array comparitive genomic hybridization, bronchioloalveolar carcinoma, non-small-cell lung carcinoma, prognostic markers
Project description:Bronchioloalveolar carcinoma (BAC), a subtype of lung adenocarcinoma (ADC) without stromal, vascular, or pleural invasion, is considered an in situ tumor with a 100% survival rate. However, the histological criteria for invasion remain controversial. BAC-like areas may accompany otherwise invasive adenocarcinoma, referred to as mixed type adenocarcinoma with BAC features (AWBF). AWBF are considered to evolve from BAC, representing a paradigm for malignant progression in ADC. However, the supporting molecular evidence remains forthcoming. Here, we have studied the genomic changes of BAC and AWBF by array comparative genomic hybridization (CGH). We used submegabase-resolution tiling set array CGH to compare the genomic profiles of 14 BAC or BAC with focal area suspicious for invasion with those of 15 AWBF. Threshold-filtering and frequency-scoring analysis found that genomic profiles of noninvasive and focally invasive BAC are indistinguishable and show fewer aberrations than tumor cells in BAC-like areas of AWBF. These aberrations occurred mainly at the subtelomeric chromosomal regions. Increased genomic alterations were noted between BAC-like and invasive areas of AWBF. We identified 113 genes that best differentiated BAC from AWBF and were considered candidate marker genes for tumor invasion and progression. Correlative gene expression analyses demonstrated a high percentage of them to be poor prognosis markers in early stage ADC. Quantitative PCR also validated the amplification and overexpression of PDCD6 and TERT on chromosome 5p and the prognostic significance of PDCD6 in early stage ADC patients. We identified candidate genes that may be responsible for and are potential markers for malignant progression in AWBF. Keywords: array comparitive genomic hybridization, bronchioloalveolar carcinoma, non-small-cell lung carcinoma, prognostic markers Array comparitive genomic hybridization analysis of 29 Lung Adenocarcinomas with Bronchioalveolar Features.
Project description:This series represents the data set of Array CGH from the paper (submit for publication): “Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas. Mestre et all. ” and it's web supplement. The molecular nature of many secondary events in the pathogenesis of B-cell non Hodgkin lymphoma (B-NHL) remains unknown. We used high-resolution CGH to BAC microarrays to characterize the genomes of 48 B-cell non-Hodgkin lymphoma (B-NHL) cell lines of different origins. Array CGH identified, on average, 20 genomic alterations per cell line, including regional gains and losses as well as previously uncharacterized aberrations. Different genomic patterns were observed among the B-NHL subtypes. To search for possible oncogenic target genes, gene expression profiling was performed in the cell lines models. Integrative genomic and gene expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated twenty homozygous deletions at seven chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Our microarray strategy has identified novel candidate suppressors inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes. Keywords: Array CGH, B-cell non-Hodgkin lymphoma, genomic amplification, homozygous deletion
Project description:Genomic DNA from sporadic breast tumours was isolated and analysed using array CGH. The NKI 1MB BAC/PAC micro array was used to identify chromosomal aberrations of all tumours. Keywords: sporadic breast tumour, CGH
Project description:Genomic DNA from sporadic breast tumours was isolated and analysed using array CGH. The NKI 1MB BAC/PAC micro array was used to identify chromosomal aberrations of all tumours. Other profiles are located at: GSE9114 Keywords: sporadic breast tumour, CGH.
Project description:We present the first computational approach to reconstruct the sequence of copy number alterations driving carcinogenesis from the analysis of several tumor samples of a same patient. Applied to BAC array-CGH and SNP array data from bladder and breast cancers, this method proved highly valuable to establish the clonal relationships between primary tumors and recurrences and to identify the chromosome aberrations at the initiation of tumorigenesis. Keywords: Comparative Genomic Hybridization
Project description:Seventy blastomeres from fourteen frozen-thawed supernumerary human preimplantation embryos were disassociated and genomic was amplified using Multiple Displacement Amplification. BAC array-CGH was performed on the amplified products.
Project description:DNA copy number analysis of 67 fresh frozen chondrosarcoma biopsies using 32k BAC and 244k oligo array CGH. Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Although rare, recurrent amplifications were found at 8q24.21-q24.22 and 11q22.1-q22.3, and homozygous deletions of loci previously implicated in chondrosarcoma development affected the CDKN2A, EXT1 and EXT2 genes. Keywords: chondrosarcoma, array comparative genomic hybridization