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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 01, 2008 |
| Title |
Whole-Genome Profiling in Liposarcomas Reveals Genetic Alterations Common to Specific Telomere Maintenance Mechanisms |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by SNP array
SNP genotyping by SNP array
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| Summary |
Telomere attrition ultimately leads to the activation of protective cellular responses such as apoptosis or senescence. Impairment of such mechanisms can allow continued proliferation despite the presence of dysfunctional telomeres. Under such conditions, high levels of genome instability are often engendered. Data from both mouse and human model systems indicate that a period of genome instability might facilitate tumorigenesis. Here, we employ a liposarcoma model system to assay telomere maintenance mechanism-specific genetic alterations. A multiassay approach was used to assess the telomere maintenance mechanism(s) active in tumors. Genomic DNA from these samples was then analyzed by high resolution DNA mapping array in order to identify genetic alterations. Our data reveal a higher level of genome instability in ALT-positive tumors as compared with telomerase-positive tumors, whereas tumors lacking both mechanisms have relatively low levels of genome instability. The bulk of the genetic changes are amplifications, regardless of the mode of telomere maintenance employed. We also identified genetic changes specific to the ALT mechanism, e.g., deletion of chromosome 1q32.2-q44, as well as changes that are underrepresented amongst ALT-positive tumors, such as amplification of chromosome 12q14.3-q21.2. Taken together, these studies provide insight into the molecular pathways involved in the regulation of ALT and reveal several loci that might be exploited either as prognostic markers or targets of chemotherapeutic intervention.
Keywords: genotype, genome instability, copy number alteration, liposarcoma, ALT, telomerase, telomere
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| Overall design |
Goal: To study telomere maintenance and genetic alterations in liposarcoma using Affymetrix Mapping 50K Xba 240 GeneChip.
Brief description: Telomere attrition ultimately leads to the activation of protective cellular responses such as apoptosis or senescence. Impairment of such mechanisms, however, can allow continued proliferation despite the presence of dysfunctional telomeres. Under such conditions, high levels of genome instability are often engendered. Data from both mouse and human model systems indicate that a period of genome instability might facilitate tumorigenesis. The high-density SNP-based microarrays (e.g., Affymetrix 100K arrays) can detect deletions, amplifications, and loss-of-heterozygosity on a genome in the liposarcoma samples. Chromosomal alterations of liposarcoma should provide insight into the molecular pathways involved in the regulation of ALT and reveal several loci that might be exploited either as prognostic markers or targets of chemotherapeutic intervention.
Quality control steps taken:
a. PCR-based quality assessment of liposarcoma tissue genomic DNA
b. Nanodrop analysis of preprocessed DNA prior to array hybridization
c. Analysis of array call rates following hybridization (array experiments giving call rates of less than 80% were routinely repeated)
Data extraction and processing protocols
a. Image scanning hardware and software, and processing procedures and parameters: SNP array hybridization was detected using a GCS3000 scanner (Affymetrix). SNP calls and signal quantification were obtained with Gene Chip Operating System (GCOS) 1.2 and Affymetrix GDAS 3.0 with Dynamic Model Mapping Analysis by default settings (0.25) for both homozygote and heterozygote call thresholds. Copy number analyses were carried out using Affymetrix Chromosome Copy Number Analysis Tool (CNAT) 2.1 with a default genomic smoothing window setting of 0.5 Mb.
b. Normalization, transformation and data selection procedures and parameters. Array data was normalized by a reference data set with CNAT.
c. Definition of chromosomal aberration, amplification, deletion and LOH used for data interpretation: These definitions and their algorithms were described in detail by Huang, et al: Whole genome DNA copy number changes identified by high density oligonucleotide arrays. Hum Genomics. 2004 May;1(4):287-99.
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| Citation(s) |
17909028 |
| Submission date |
Jun 06, 2007 |
| Last update date |
Dec 22, 2017 |
| Contact name |
Jay Johnson |
| E-mail(s) |
johnsja4@memorialhealth.com
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| Organization name |
Memorial Health University Medical Center
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| Street address |
4700 Waters Ave
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| City |
Savannah |
| State/province |
GA |
| ZIP/Postal code |
31404 |
| Country |
USA |
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| Platforms (1) |
| GPL2005 |
[Mapping50K_Xba240] Affymetrix Human Mapping 50K Xba240 SNP Array |
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| Samples (25)
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| GSM197635 |
Tumor 1, Grade 1, Age 66, ALT-positive |
| GSM198454 |
Tumor 2, Grade 1, Age 65, ALT-positive |
| GSM198455 |
Tumor 3, Grade 1, Age 53, ALT-positive |
| GSM198510 |
Tumor 4, Grade 1, Age 73, ALT-positive |
| GSM198600 |
Tumor 5, Grade 1, Age 64, ALT-positive |
| GSM198601 |
Tumor 7, Grade 1, Age 72, ALT-positive |
| GSM198614 |
Tumor 8, Grade 1, Age 76, neither ALT- nor telomerase-positive |
| GSM198615 |
Tumor 9, Grade 1, Age 49, telomerase-positive with an intermediate ALT-phentype |
| GSM198666 |
Tumor 10, Grade 1, Age 44, neither ALT- or telomerase-positive |
| GSM198667 |
Tumor 11, Grade 1, Age 73, neither ALT- or telomerase-positive |
| GSM198668 |
Tumor 15, Grade 1, Age 64, telomerase-positive |
| GSM198669 |
Tumor 20, Grade 1, Age 74, telomerase-positive |
| GSM198670 |
Tumor 23, Grade 2, Age 52, telomerase-positive |
| GSM198671 |
Tumor 28, Grade 1, Age 57, neither ALT- or telomerase-positive |
| GSM198672 |
Tumor 29, Grade 1, Age 59, neither ALT- or telomerase-positive |
| GSM198673 |
Tumor 30, Grade 3, Age 68, ALT-positive |
| GSM198674 |
Tumor 31, Grade 3, Age 78, neither ALT- or telomerase-positive |
| GSM198675 |
Tumor 32, Grade 3, Age 44 |
| GSM198676 |
Tumor 26, Grade 1, Age 57, neither ALT- or telomerase-positive |
| GSM198677 |
Tumor 26R1, Grade 2, Age 60, neither ALT- or telomerase-positive This tumor is a recurrence of Tumor 26 |
| GSM198678 |
Tumor 26R2, Grade 2, Age 60, telomerase-positive This tumor is a recurrence of Tumor 26R1 |
| GSM198679 |
Tumor 27, Grade 1, Age 69, telomerase-positive |
| GSM198680 |
Tumor 27R1, Grade 2, Age 69, telomerase-positive This sample is a recurrence of Tumor 27 |
| GSM198681 |
Tumor 27R2, Grade 2, Age 70, telomerase-positive This sample is a recurrence of Tumor 27R1 |
| GSM198682 |
Normal, Age 44 Normal adipose tissue obtained from the same patient as Tumor 32 |
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| Relations |
| BioProject |
PRJNA100869 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8046_RAW.tar |
339.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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