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| Status |
Public on Apr 27, 2011 |
| Title |
Genomic profiling of hereditary epithelial ovarian cancer using tiling resolution array CGH |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
Heredity is a major risk factor for ovarian cancer, but many families escape detection. Refined diagnosis of ovarian cancers linked to the breast and ovarian cancer (HBOC) syndrome and the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome would allow cancer prevention in high risk families. In order to delineate genetic profiles of hereditary ovarian cancer, we applied genome wide array comparative genomic hybridization to 24 sporadic tumors, 12 HBOC associated tumors (BRCA1 mutations) and eight HNPCC associated tumors (mismatch repair gene mutations). Unsupervised cluster analysis identified two distinctive clusters related to genetic complexity. Most sporadic and HBOC associated tumors had complex genetic profiles with multiple gains and losses with an average of 41% of the genome altered, whereas mismatch repair defective tumors had stable genetic profiles, with an average of 18% of the genome altered. Losses of 4q34, 13q12-q32 and 19p13 were overrepresented in the HBOC subset, gains of chromosomes 17 and 19 characterized the HNPCC tumors and gains of 20q11 were more common in the sporadic tumors. The genetic distinction between HBOC and HNPCC associated ovarian cancer suggests that genetic profiles can be applied for refined classification of hereditary cases and reflects tumor development along different genetic pathways.
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| Overall design |
DNA was extracted from formalin fixed, paraffin embedded tumor tissue according to protocols from the UCSF Waldman Laboratory, San Francisco, CA, USA (http://cc.ucsf.edu/people/waldman/Protocols/paraffin.html), with an additional purification step using Phase Lock Gel tubes (Eppendorf AG, Hamburg, Germany). DNA quality was assessed using a Ready-To-Go RAPD analysis kit (GE Healthcare, Little Chalfont, UK) with primers 5’-AATCGGGCTG-3’ and 5’-GAACGGGTG-3’. PCR products were validated on a Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA). Tiling 32k BAC microarrays, with contiguous genome wide coverage, were produced at the Microarray DNA Resource Centre, SCIBLU Genomics, Department of Oncology, Lund University, Sweden (http://www.lth.se/sciblu). Labeling and hybridization were performed in short, 2-8 μg tumor DNA and 2 µg reference DNA (Promega Corporation, Madison, WI, USA) were labeled with Cy3-dCTP and Cy5-dCTP, using BioPrime Array CGH Genomic Labeling System (Invitrogen Life Technologies, Carlsbad, CA, USA). Tumor and reference DNA were pooled and mixed with Human COT-1 DNA (Invitrogen). Hybridizations were conducted using the MAUI® Hybridization System (BioMicro systems Inc, Salt Lake City, UT, USA) and the slides were scanned in an Agilent Microarray Scanner (Agilent Technologies).
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| Contributor(s) |
Domanska K, Malander S, Staaf J, Karlsson A, Borg A, Jönsson G, Nilbert M |
| Citation(s) |
20811668 |
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| Submission date |
Apr 25, 2011 |
| Last update date |
Mar 23, 2012 |
| Contact name |
Katarina Bartuma |
| E-mail(s) |
katarina.bartuma@med.lu.se
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| Organization name |
department of Oncology
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| Street address |
Barn garan 2b
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| City |
Lund |
| ZIP/Postal code |
221 85 |
| Country |
Sweden |
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| Platforms (1) |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA140677 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE28850_RAW.tar |
121.9 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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