Dataset Information

High resolution genomic analysis of 18q- using oligo-microarray comparative genomic hybridization (aCGH).

ABSTRACT: The advent of oligonucleotide array comparative genomic hybridization (aCGH) has revolutionized diagnosis of chromosome abnormalities in the genetics clinic. This new technology also has valuable potential as a research tool to investigate larger genomic rearrangements that are typically diagnosed via routine karyotype. aCGH was used as a tool for the high-resolution analysis of chromosome content in individuals with known deletions of chromosome 18. The aim of this study was to clarify the precise location of the breakpoints as well as to determine the presence of occult translocations creating additional deletions and duplications. One hundred eighty-nine DNA samples from individuals with 18q deletions were analyzed. No breakpoint clusters were identified, as no more than two individuals had breakpoints within 2 kb of each other. Only two regions of 18q were never found to be haploid, suggesting the existence of haplolethal genes in those regions. Of the individuals with only a chromosome 18 abnormality, 17% (n = 29) had interstitial deletions. Six percent (n = 11) had a region of duplication immediately proximal to the deletion. Eight percent (n = 15) had more complex rearrangements with captured (non-18q) telomeres thus creating a trisomic region. The 15 captured telomeres originated from a limited number of other telomeres (4q, 10q, 17p, 18p, 20q, and Xq). These data were converted into a format for ease of viewing and analysis by creating custom tracks for the UCSC Genome Browser. Taken together, these findings confirm a higher level of variability and genomic complexity surrounding deletions of 18q than has previously been appreciated.

SUBMITTER: Heard PL

PROVIDER: S-EPMC2731576 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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High resolution genomic analysis of 18q- using oligo-microarray comparative genomic hybridization (aCGH).

Heard Patricia L PL Carter Erika M EM Crandall Analisa C AC Sebold Courtney C Hale Daniel E DE Cody Jannine D JD

American journal of medical genetics. Part A 20090701 7

The advent of oligonucleotide array comparative genomic hybridization (aCGH) has revolutionized diagnosis of chromosome abnormalities in the genetics clinic. This new technology also has valuable potential as a research tool to investigate larger genomic rearrangements that are typically diagnosed via routine karyotype. aCGH was used as a tool for the high-resolution analysis of chromosome content in individuals with known deletions of chromosome 18. The aim of this study was to clarify the prec ...[more]

PMID: 19533772

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Project description:Neuroblastoma (NB) is an aggressive tumor that affects both infants and children. The disease outcome is greatly influenced by age of patient, stage, chromosome copy number aberrations (CNAs) and gene expression abnormalities. We analyzed, by microarray technology, genome and transcriptome of 3 groups of tumors of patients with metastatic disease: G1, stage 4S and MYCN single copy; G2, stage 4 younger than 18 months of age, MYCN single copy with no disease progression and G3, stage 4, older than 19 months, with unfavorable outcome. We found an accumulation of structural copy number aberrations (CNAs) in G3 whereas G1 tumors had mostly numerical (N) CNAs and G2 showed an intermediate behavior. Pair wise comparisons demonstrated that the average of N CNAs significantly decreased from G1 to G2 to G3 (9.6 G1 < 7.2 G2 < 3.6 G3); in contrast S CNAs significantly increased in G3 (0.7 G1 < 3.7 G2 < 7.0 G3). Interestingly, we observed several intra-chromosomal rearrangements in G3 tumors on chromosomes not usually involved in NB. Excluding MYCN amplified tumors by G3 we found a high frequency of S CNAs in this group. Gene expression analysis showed a deregulation of downstream genes of Ras and Rho signaling pathway among the 3 groups. It has been also observed a progressive switch off of development and adhesion genes and a switch on of cell cycle genes from G1 to G2 to G3. Moreover, the telemorase genes were significantly expressed in G3 with respect to remaining groups. Present data show an accumulation of S CNAs from stage 4S to 4. The deregulation of genes Rho/Ras pathway may explain the increase of tumor aggressiveness from G1 to G2 to G3. The increase of cell cycle and telomerase genes expression associated with G3 would provide unlimited replicative potential for these tumors and may be responsible for accumulation of S CNAs. Finally, we can argue that accumulation of structural aberrations and gene deregulation is age-dependent and it is associated with a more aggressive tumor phenotype.

Dataset Information

High resolution genomic analysis of 18q- using oligo-microarray comparative genomic hybridization (aCGH).

Publications

High resolution genomic analysis of 18q- using oligo-microarray comparative genomic hybridization (aCGH).

Similar Datasets

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