Identification of novel copy number alterations by high-resolution aCGH from FFPE cutaneous melanoma samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Toma Tebaldi
PROVIDER: E-GEOD-45354 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The aim of the study was to address the concept of field cancerization in oral cancer. The presence of genomic aberrations, indicative of chromosomal instability (CIN), in oral distant fields (ODFs) of visually normal and non-dysplastic mucosa at the mirror image from concomitant oral potentially malignant lesions (OPMLs) was investigated. This pilot study comprised 16 OPMLs (8 without dysplasia, nd-OPMLs; 8 with dysplasia, d-OPMLs) and 16 ODFs. DNA diploid (DNA Index, DI=1) and aneuploid (DIM-bM-^IM- 1) sublines were detected by high resolution DNA-flow cytometry (FCM) at (hr DNA-FCM) using DAPI stained nuclei suspensions. Nuclei with different DIs were FCM-sorted in order to enrich the epithelial component and to obtain genomic DNA for high resolution oligonucleotide array-Comparative Genomic Hybridization (a-CGH) analysis to provide a genome-wide measurement of DNA copy number aberrations (CNAs). The frequencies of DNA aneuploidy in ODFs and OPMLs were 6.2% and 43.8%, respectively (p=0.037). ODFs and nd-OPMLs were all near-diploid (DIM-bM-^IM- 1 and DIM-bM-^IM-$1.4), while d-OPMLs were also high-aneuploid (DI>1.4). CNA averages were 2.3 in ODFs (1.5 for nd-OPMLs and 3.1 for d-OPMLs), and 7.325 in OPMLs (3.0 in nd-OPMLs; 11.6 in d-OPMLs). CNAs were present in the DNA diploid sublines and often the same CNAs were observed in both ODFs and corresponding OPMLs DNA aneuploid sublines and CNAs in the present series of 16 ODFs are likely to represent early events of the natural history of oral carcinogenesis and to indicate an early onset of the field effect cancerization. Moreover, gains within 20q13.33-qter, 7p22.2-pter and 16p13.3-pter chromosomal regions in ODFs and in the relative OPMLs suggest that specific genes localized in these regions (RTEL1, MAD1L1 and TEL2) might contribute to the ODF/d-OPML transition. We analyzed: 8 samples of oral potentially malignant lesions with dysplasia, 8 samples of oral potentially malignant lesions without dysplasia and for each patient a corresponding oral distant field of visually normal mucosa.
2011-12-21 | E-GEOD-28906 | biostudies-arrayexpress
Project description:Lymph-node (LN) metastases predict for high recurrence rates in breast cancer patients. Eradication of micro-metastatic tumor cells is the primary goal of adjuvant systemic treatment. Decisions regarding systemic treatment depend largely on primary tumor characteristics rather than on characteristics of their LN metastases. However, it remains unclear to what extent LN metastases, having already metastasized locally, resemble their primary breast tumors and as such will be eradicated by the systemic therapy chosen. In this study we investigated the genetic differences between primary breast cancers and their paired LN metastases using array comparative genomic hybridization analyses on a high resolution 720K Nimblegen platform. Thus far, no metastasis-specific genomic aberrations have been identified. We hypothesized that this is due to low-resolution platforms and lack of stratification on breast cancer subtypes (specifically, triple-negative (TN) versus luminal). Furthermore, we speculated that as TN tumours are known to be more genetically unstable, their LN metastases would show an increase in random copy number aberrations (CNAs). Therefore, we studied 10 primary TN breast tumourM-bM-^@M-^SLN pairs and 10 luminal pairs and found that all LN metastases clustered nearest to their matched tumour except for two. These two were explained by poor hybridization quality and, interestingly, the presence of two histological components in one tumour. We found no significantly altered CNAs between pairs in the whole group, nor when subdivided over subtypes; neither did we find a CNA increase in LN metastases compared to primary tumours within the TN subgroup, suggesting most CNAs are functional and not random. Our findings suggest a strong clonal relationship between primary breast tumours and its LN metastases and support the use of the primary tumor characteristics to guide adjuvant systemic chemotherapy in breast cancer patients, since primary tumors and their subsequent LN metastases seem remarkably similar, at least prior to treatment. The experiment contains 20 paired primary breast cancer samples with their lymph node metastases, analysed on a 720 whole genome CGH array. Additionally, for one sample its two distinct histological subpopulations were analysed on the same platform.
2014-01-01 | E-GEOD-38888 | biostudies-arrayexpress
Project description:The mucosae of the oral cavity are different at the histological level but are all exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. exposed to common genotoxic agents. As a result of this exposure, changes in the mucosal epithelia develop giving rise to Oral Potentially Malignant Lesions (OPMLs), which with time may in turn progress to Oral Squamous Cell Carcinomas (OSCCs). Therefore, much effort should be devoted to identify features able to predict the likeliness of progression associated with an OPML. Such features may be helpful in assisting the clinician to establish both appropriate therapies and follow-up schedules. Here, we report a pilot study that compared the anatomical subsites of OPMLs development with occurrence of DNA aneuploidy and chromosomal copy number aberrations (CNAs). Multiple samples from histologically diagnosed OPMLs were processed for high resolution DNA flow cytometry (hr DNA-FCM) in order to determine the relative DNA content expressed by the DNA index (DI). Additionally, array-Comparative Genomic Hybridization (a-CGH) analysis was performed on FCM-sorted nuclei subpopulations based on DI values. Tongue OPMLs were more frequently associated with DNA aneuploidy and CNAs than OPMLs arising from all the other mucosal subsites. We suggest that the follow-up and the management of the patients with tongue OPMLs should receive a distinctive special attention. Clearly, this conclusion should be validated in a prospective clinical study. We analyzed: 19 samples (4 aneuploid and 15 diploid components) deriving from oral potentially malignant lesions without dysplasia obtained of 16 patients; 14 samples (2 aneuploid and 12 diploid components) deriving from oral potentially malignant lesions with dysplasia obtained from 11 patients (two patients had multiple dysplastic lesions); 2 samples from visually normal mucosa in the near field obtained from two patients with dysplastic lesions. All the aneuploid samples had a purity of at least 90%.
2011-10-19 | E-GEOD-28868 | biostudies-arrayexpress
Project description:The aim of this study is to determine copy number variations in the multiple myeloma patients, which were positive for BCL1/JH t(11;14)(q13;q32) translocation. Identification of common chromosomal aberrations representing the t(11;14)(q13;q32) subtype is possible by comparing the microarray data across all the samples under studied. Eight multiple myeloma samples were analyzed. Each sample was compared against normal control (match with patient's race and gender), which was pooled from ten healthy individuals.
2012-12-31 | E-GEOD-33757 | biostudies-arrayexpress
Project description:The aim of this study is to identify copy number variations in multiple myeloma patients from the 3 major ethnic groups (Malays, Chinese and Indians) in Malaysia. Identification of common chromosomal aberrations and their degree of penetrance is possible by comparing the microarray data across all the samples under studied. 63 multiple myeloma samples were analyzed. Each sample was compared against normal control (match with patient's race and gender), which was pooled from ten healthy individuals.
2015-12-31 | E-GEOD-44745 | biostudies-arrayexpress
Project description:To investigate the cytogenetic and large-scale chromosomal changes in involuted or non-involuted microGISTs using post-whole genome amplification (WGA) FFPE DNA materials Sixteen patients, total 19 FFPE tumor samples (block storage time 4 months to 9 years), including 16 microGISTs and 3 GISTs larger than 1 cm from the same patients harboring microGISTs. All FFPE tumor samples underwent DNA extraction and WGA (modified degenerate oligonucleotide PCR (DOP) method, provided by Sigma). For each tumor sample, a post-WGA DNA extract from the normal tissue in the same block (or block from the same patient with a block storage time differences less than 2 years) was obtained for tumor sample DNA co-hybridization. Tumor and normal areas of interest were marked and collected from 5- to 10-micron unstained or hematoxylin-stained sections by manual or laser (PixCell IITM, Arcturus Bioscience, CA, USA) microdissection. DNAs were then extracted. WGA was performed using GenomePlex® Tissue Whole Genome Amplification WGA5 kit (Sigma, Saint Louis, MO, USA; http://www.sigmaaldrich.com/) in parallel in accordance with the manufacturer's protocols. At least four independent experiments were concurrently performed per template amplification. Four separate WGA reaction products were pooled for each sample.
2011-12-31 | E-GEOD-28469 | biostudies-arrayexpress
Project description:Using high-resolution, array-based comparative genomic hybridization (aCGH), we explored genomic alterations in 40 fresh-frozen ACC samples, the largest cohort to date, with the aims to: (1) identify recurrent CNAs in ACC; (2) identify novel candidate target genes; and (3) correlate recurrent CNAs with tumour grade and other clinical parameters to identify potential clinically useful biomarkers. High-resolution aCGH on fresh frozen tissue from 40 ACCs.
2012-12-31 | E-GEOD-34816 | biostudies-arrayexpress
Project description:Purpose: Only a limited number of genetic studies have been performed in primary central nervous system lymphomas (PCNSL), partly due to the rarity of the tumors and the very limited amount of available tissue. In this report, we present the first molecular characterization of copy-number abnormalities (CNA) of newly diagnosed PCNSL by array-based comparative genomic hybridization in formalin fixed paraffin embedded (FFPE) specimens and compare the results with matched frozen tumor specimens. Experimental design: We performed array-based comparative genomic hybridization (aCGH) in FFPE tissues from PCNSL. Results were compared with matched paired frozen tumors. Results: Our analysis confirmed the good to fair quality and reliability of the data generated from limited amounts of tumoral FFPE tissue. Overall, all PCNSL cases were characterized by highly complex karyotypes with a median of 23 copy-number abnormalities (CNA) per patient (range 17-47). Overall, 20 chromosomal regions were recurrently found in more than 40% of cases. Deletions of 6p21, 6q, 9p21.3 and gain of 12q12-q24.33 were the commonest CNA. Other minimal affected regions were defined, and novel recurrent CNAs affecting single genes were identified in 3q26.32 (TBL1XR1) and 8q12.1 (TOX). Conclusions: The results obtained are encouraging. Larger archival tissue collections can now be analyzed in order to complement the still fragmented knowledge we have of the genetic basis of the PCNSL. We included samples from 7 PCNSL patients. In 6 out of these 7 PCNSL patients (cases B – G), aCGH experiments were performed in DNA samples obtained from both snap-frozen and FFPE tissues for assay quality comparative purposes. In the remaining sample (case A), only frozen sample was analyzed.
2012-04-29 | E-GEOD-28952 | biostudies-arrayexpress
Project description:In this study, we evaluation of incidence of copy number abnormalities (CNAs) with high-desity CGH+SNP microarrays in cohort 26 patients with cervical tumors. Incidence of CNAs was copmared with clinical prognostic factors.
2014-04-01 | E-MTAB-2293 | biostudies-arrayexpress
Project description:In this study, we sought to indentify stable individual traits in developing metastatic melanoma, assess their stability in time, and analyze typical dynamics and common trends of genomic changes in individual cases of late stage metastatic cancer. To this end, we compared consecutive recurrent metastases developed by a special group of eight individuals with advanced metastatic melanoma, all developing several recurrent metastases over several months to years of natural disease evolution. Twenty-six recurrent melanoma metastases were surgically isolated from 8 patients experiencing relapse after one or more successful treatment intervention(s) with no signs of residual disease. Patients experiencing recurrent metastases were labeled with capital letters; M-bM-^@M-^\AM-bM-^@M-^], M-bM-^@M-^\BM-bM-^@M-^], M-bM-^@M-^\CM-bM-^@M-^], etc., their subsequent metastases as M-bM-^@M-^\A/1M-bM-^@M-^], M-bM-^@M-^\A/2M-bM-^@M-^], M-bM-^@M-^\B/1M-bM-^@M-^], M-bM-^@M-^\B/2M-bM-^@M-^], etc., while synchronous metastases in a given patient were labeled as M-bM-^@M-^\A/1aM-bM-^@M-^], M-bM-^@M-^\A/1bM-bM-^@M-^] etc. Another 22 melanoma cell lines isolated and maintained as above were expanded from melanoma patients with rapid disease curse, for whom only one metastasis was available. As no extended follow up was possible in these cases, the cell lines are considered representative of random time points in the natural course of metastatic melanoma. These cell lines were labeled with Arabic numbers, as M-bM-^@M-^\1M-bM-^@M-^], M-bM-^@M-^\2M-bM-^@M-^], M-bM-^@M-^]3M-bM-^@M-^], etc.
2013-12-31 | E-GEOD-38137 | biostudies-arrayexpress