Copy number analysis of familial and sporadic Epithelial Ovarian Carcinomas (EOC) from FFPE tissue on high resolution Agilent platform.
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Maria GarcÃa
PROVIDER: E-GEOD-41253 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:BACKGROUND: Infection with high-risk types of human papillomavirus (hrHPV) is associated with cervical, anogenital and oropharyngeal cancers. A role for hrHPV in lung cancer has been proposed, although previous reports on the contribution of hrHPV infection to lung cancer have provided contradictory results. The current study evaluated hrHPV prevalence in lung tumor specimens of different histological subtypes in a Western study population using a validated test algorithm for hrHPV detection in formalin-fixed paraffin-embedded (FFPE) tumor specimen (i.e., GP5+6+-PCR and p16INK4A immunohistochemistry). MATERIALS AND METHODS: Tumor tissue specimens from 228 lung cancer patients were subjected to GP5+6+-PCR and p16INK4A immunohistochemistry. hrHPV-positive tumors were further characterized using genotyping of GP5+/6+-PCR products, HPV E7 transcript analysis, loss of heterozygosity (LOH) analysis and array comparative genomic hybridization (arrayCGH), and the clinical history of patients was retrieved. RESULTS: Three patients (3/228, 1.3%) with hrHPV-positive lung tumors were identified, revealing hrHPV types 16, 18 and 33, respectively. All three patients (1 male, 2 females) had a history of hrHPV-associated disease; two cervical carcinoma, and one oropharyngeal carcinoma. Further characterization revealed identical hrHPV genotype, pattern of p16INK4A expression, HPV E7 mRNA expression, and genomic aberrations in the individual pairings of lung tumor and foregoing hrHPV-associated cancer. CONCLUSION: The present study found molecular evidence that supports association of hrHPV in lung cancer with the presence of pulmonary metastasis of a hrHPV-positive cancer that originated elsewhere, and not with primary lung cancer in a Western population. 2 lung cancer samples (FFPE), 1 cervical cancer sample (FFPE), 1 head and neck cancer sample (FFPE)
2013-07-01 | E-GEOD-40777 | biostudies-arrayexpress
Project description:Chromosomal instable colorectal cancer is marked by specific large chromosomal copy number aberrations. Recently, focal aberrations of 3Mb or smaller have been identified as a common phenomenon in cancer. Inherent to their limited size, these aberrations harbour one or few genes. The aim of this study is to identify recurrent focal chromosomal aberrations and their candidate driver genes in a well defined series of stage II colon cancers and assess their potential clinical relevance. High resolution DNA copy number profiles were obtained from 38 formalin fixed paraffin embedded colon cancer samples with matched normal mucosa as a reference using array comparative genomic hybridization. In total, 81 focal chromosomal aberrations were identified that harboured 177 genes. Statistical validation of focal aberrations and identification of candidate driver genes was performed by enrichment analysis and mapping copy number and mutation data of colorectal-, breast-, pancreatic cancer and glioblastomas to loci of focal aberrations in stage II colon cancer. This analysis demonstrated a significant overlap with previously identified focal amplifications in colorectal cancer, but not with cancers from other sites. In contrast, focal deletions seem less tumour type specific since they also show significant overlap with focal deletions of other sites. Focal deletions detected are significantly enriched for cancer genes and genes frequently mutated in colorectal cancer. The mRNA expression of these genes is significantly correlated with DNA copy number status, supporting the relevance of focal aberrations. Loss of 5q34 and gain of 13q22.1 were identified as independent prognostic factors of survival in this series of patients. In conclusion, focal chromosomal copy number aberrations in stage II colon cancer are enriched in cancer genes which contribute to and drive the process of colorectal cancer development. DNA copy number status of these genes correlate with mRNA expression and some are associated with clinical outcome. 38 Stage II colorectal cancer (CRC) tissue samples (FFPE) of which 19 were done on expression arrays. One sample (Stage II colorectal cancer tissue samples (FFPE) 26) was also done on the 135K NimbleGen array. Fresh frozen and FFPE of the same CRC stage I sample was done on 105K agilent. The fresh frozen was across array in silico set out against a pool of blood of 18 healthy females.
2010-04-19 | E-GEOD-17047 | biostudies-arrayexpress
Project description:Background: Around 30% of all stage II colon cancer patients will relapse and die of their disease. At present no objective parameters for identification of high-risk stage II colon cancer patients, who will benefit from adjuvant chemotherapy, are established. With traditional histopathological features definition of high-risk stage II colon cancer patients is inaccurate. Therefore more objective and robust markers for prediction of relapse are needed. DNA copy number aberrations have proven to be robust prognostic markers, but have not been investigated for this specific group of patients. The aim of the present study is to identify chromosomal aberrations that can predict relapse of tumor in patients with stage II colon cancer. Materials and Methods: DNA was isolated from 40 formaldehyde fixed paraffin embedded stage II colon cancer samples with extensive clinicopathological data. Samples where hybridized using Comparative Genomic Hybridization (CGH) arrays to determine DNA copy number changes and microsatellite stability was determined by PCR. To analyze differences between stage II colon cancer patients with and without relapse of tumor a Wilcoxon rank-sum test was implemented with multiple testing correction Results: Patients with stage II colon cancer who had relapse of disease showed significant more losses on chromosome 4, 5, 15q, 17q and 18q. When microsatellite stable (MSS) patients were analyzed separately, only losses on chromosome 4q22.1-4q35.2 predicted worse outcome in stage II colon cancer patients. No differences in clinicopathological characteristics between patients with and without relapse were observed. Conclusion: Losses on 4q22.1-4q35.2 predict worse outcome in MSS stage II colon cancer patients and may aid in the selection of patients for adjuvant therapy. 40 Stage II colorectal cancer (CRC) tissue samples (FFPE), 16 with and 24 without relapse of tumor
2010-07-13 | E-GEOD-17181 | biostudies-arrayexpress
Project description:Formalin-fixed, paraffin-embedded (FFPE) archival tissue is an important source of DNA material. The most commonly used technique to identify copy number aberrations from chromosomal DNA in tumorigenesis is array comparative genomic hybridization (aCGH). Although copy number analysis using DNA from FFPE archival tissue is challenging, several research groups have reported high quality and reproducible DNA copy number results using aCGH. Aim of the present study is to compare aCGH platforms suitable for copy number analysis using FFPE derived DNA. Two dual channel aCGH platforms (Agilent and NimbleGen) and a single channel SNP based platform (Affymetrix), were evaluated using seven FFPE colon cancer samples, median absolute deviation (MAD), deflection, signal-to-noise ratio (SNR) and DNA input requirements were used as quality criteria. Large differences were observed in MAD values and deflection between platforms; Agilent and NimbleGen showed better MAD values (0.13 for both) compared to Affymetrix (0.22). Contrary, Affymetrix showed a better deflection of 0.94, followed by 0.71 for Agilent and 0.51 for NimbleGen. Since the deflection compensates for the MAD the Signal to Noise Ratios (SNR) were comparable; Agilent ranks first, Affymetrix second and NimbleGen third with SNRs of 3.9, 3.6 and 3.3 respectively. DNA input amounts of 40ng are sufficient for high quality profiles with Affymetrix. For Agilent DNA input amounts of 50ng are sufficient for high quality profiles. For results of similar quality NimbleGen requires at least 100ng. Copy number analysis using DNA derived from FFPE archival material is feasible and shows reproducible results on high-resolution copy number platforms. Input amounts of DNA from FFPE material lower than recommended still yield high quality profiles without additional amplification steps. Overall study comprises 6 samples analyzed across three platforms with an additional dilution range (5 concentrations) of a seventh sample on two platforms. This Series represents Agilent platform-derived data.
2012-01-17 | E-GEOD-30121 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE30120: Three commercial array platforms compared for DNA copy number detection with DNA isolated from FFPE tissue [NimbleGen] GSE30121: Three commercial array platforms compared for DNA copy number detection with DNA isolated from FFPE tissue [Agilent] Refer to individual Series
2012-01-17 | E-GEOD-30123 | biostudies-arrayexpress
Project description:The genetic cause for PPB in association with renal tumor and small bowel polyps remains to be identified. Activation of components of the mTOR signalling pathway in the disease lesions suggests that this signal transduction route may be involved in disease pathogenesis and that rapamycin, an inhibitor of mTOR, might be effective in the treatment of PPB and associated lesions. A combination of molecular cytogenetics and gene-specific mutation screens were performed to search for an underlying genetic cause for PPB in association with small bowel polyps. Immunohistochemical analysis to measure mTOR activation was performed on tissue from renal and lung tumor and small bowel polyps from the index case
2010-04-02 | E-GEOD-15521 | biostudies-arrayexpress
Project description:Formalin-fixed, paraffin-embedded (FFPE) archival tissue is an important source of DNA material. The most commonly used technique to identify copy number aberrations from chromosomal DNA in tumorigenesis is array comparative genomic hybridization (aCGH). Although copy number analysis using DNA from FFPE archival tissue is challenging, several research groups have reported high quality and reproducible DNA copy number results using aCGH. Aim of the present study is to compare aCGH platforms suitable for copy number analysis using FFPE derived DNA. Two dual channel aCGH platforms (Agilent and NimbleGen) and a single channel SNP based platform (Affymetrix), were evaluated using seven FFPE colon cancer samples, median absolute deviation (MAD), deflection, signal-to-noise ratio (SNR) and DNA input requirements were used as quality criteria. Large differences were observed in MAD values and deflection between platforms; Agilent and NimbleGen showed better MAD values (0.13 for both) compared to Affymetrix (0.22). Contrary, Affymetrix showed a better deflection of 0.94, followed by 0.71 for Agilent and 0.51 for NimbleGen. Since the deflection compensates for the MAD the Signal to Noise Ratios (SNR) were comparable; Agilent ranks first, Affymetrix second and NimbleGen third with SNRs of 3.9, 3.6 and 3.3 respectively. DNA input amounts of 40ng are sufficient for high quality profiles with Affymetrix. For Agilent DNA input amounts of 50ng are sufficient for high quality profiles. For results of similar quality NimbleGen requires at least 100ng. Copy number analysis using DNA derived from FFPE archival material is feasible and shows reproducible results on high-resolution copy number platforms. Input amounts of DNA from FFPE material lower than recommended still yield high quality profiles without additional amplification steps. Overall study comprises 6 samples analyzed across three platforms with an additional dilution range (5 concentrations) of a seventh sample on two platforms. This Series represents NimbleGen platform-derived data.
2012-01-17 | E-GEOD-30120 | biostudies-arrayexpress
Project description:Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, is often not uniform throughout cell populations. The aim of our present study is to evaluate to what extent aCGH can detect DNA copy number alterations in a heterogeneous cell population. Reported detection limits are a compound of analytical software and laboratory technique whilst systematic evaluation is lacking, despite the importance in diagnostics and research. Detection limits were explored with DNA isolated from a patient with intellectual disability (ID) and from tumor cell line BT474. Both were diluted with increasing amounts of normal DNA to simulate different levels of cellularity. Samples were hybridized on CGH arrays containing 180880 oligonucleotides evenly distributed over the genome (space ~17kb). The ID sample has a single copy number gain of 4Mb and a single copy number loss of 7.5Mb that could both be detected with 10% mosaicism. The tumor cell line BT474 has a dual copy number gain (6 copies in a background of 4 copies) of 46Mb. This corresponds to a single copy number gain in a diploid sample and could be detected with 15% tumor cells. The diagnostic validity of these findings was verified using two clinical mosaic samples with alterations in 20% (40Mb) and 14% (34Mb) of cells. Both alterations could be accurately detected using t-statistics. In conclusion, single copy number gains and losses, down to 4Mb in as little as 10% of a cell population, can be detected by aCGH. Dilution range of breast cancer cell line BT474 used to test the detection limits of array CGH.
2012-10-21 | E-GEOD-36856 | biostudies-arrayexpress
Project description:Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, is often not uniform throughout cell populations. The aim of our present study is to evaluate to what extent aCGH can detect DNA copy number alterations in a heterogeneous cell population. Reported detection limits are a compound of analytical software and laboratory technique whilst systematic evaluation is lacking, despite the importance in diagnostics and research. Detection limits were explored with DNA isolated from a patient with intellectual disability (ID) and from tumor cell line BT474. Both were diluted with increasing amounts of normal DNA to simulate different levels of cellularity. Samples were hybridized on CGH arrays containing 180880 oligonucleotides evenly distributed over the genome (space ~17kb). The ID sample has a single copy number gain of 4Mb and a single copy number loss of 7.5Mb that could both be detected with 10% mosaicism. The tumor cell line BT474 has a dual copy number gain (6 copies in a background of 4 copies) of 46Mb. This corresponds to a single copy number gain in a diploid sample and could be detected with 15% tumor cells. The diagnostic validity of these findings was verified using two clinical mosaic samples with alterations in 20% (40Mb) and 14% (34Mb) of cells. Both alterations could be accurately detected using t-statistics. In conclusion, single copy number gains and losses, down to 4Mb in as little as 10% of a cell population, can be detected by aCGH. DNA of a chronic lymphocytic leukemia (CLL) patient with mosaic aberrations in chromosome 12.
2012-10-21 | E-GEOD-36992 | biostudies-arrayexpress
Project description:Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, is often not uniform throughout cell populations. The aim of our present study is to evaluate to what extent aCGH can detect DNA copy number alterations in a heterogeneous cell population. Reported detection limits are a compound of analytical software and laboratory technique whilst systematic evaluation is lacking, despite the importance in diagnostics and research. Detection limits were explored with DNA isolated from a patient with intellectual disability (ID) and from tumor cell line BT474. Both were diluted with increasing amounts of normal DNA to simulate different levels of cellularity. Samples were hybridized on CGH arrays containing 180880 oligonucleotides evenly distributed over the genome (space ~17kb). The ID sample has a single copy number gain of 4Mb and a single copy number loss of 7.5Mb that could both be detected with 10% mosaicism. The tumor cell line BT474 has a dual copy number gain (6 copies in a background of 4 copies) of 46Mb. This corresponds to a single copy number gain in a diploid sample and could be detected with 15% tumor cells. The diagnostic validity of these findings was verified using two clinical mosaic samples with alterations in 20% (40Mb) and 14% (34Mb) of cells. Both alterations could be accurately detected using t-statistics. In conclusion, single copy number gains and losses, down to 4Mb in as little as 10% of a cell population, can be detected by aCGH. Dilution range of DNA from a patient with an intellectual disabillity (ID) used to test the detection limits of array CGH.
2012-10-21 | E-GEOD-36989 | biostudies-arrayexpress