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Ultra-High Density SNParray in Neuroblastoma Molecular Diagnostics.

Ambros IM, Brunner C, Abbasi R, Frech C, Ambros PF - Front Oncol (2014)

Bottom Line: However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses.However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques.Single nucleotide polymorphism arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine.

View Article: PubMed Central - PubMed

Affiliation: Children's Cancer Research Institute, St. Anna Kinderkrebsforschung , Vienna , Austria.

ABSTRACT
Neuroblastoma serves as a paradigm for applying tumor genomic data for determining patient prognosis and thus for treatment allocation. MYCN status, i.e., amplified vs. non-amplified, was one of the very first biomarkers in oncology to discriminate aggressive from less aggressive or even favorable clinical courses of neuroblastoma. However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses. So called "segmental chromosomal aberrations," (SCAs) i.e., gains or losses of chromosomal fragments, can also indicate tumor aggressiveness. The clinical use of these genomic aberrations has, however, been hampered for many years by methodical and interpretational problems. Only after reaching worldwide consensus on markers, methodology, and data interpretation, information on SCAs has recently been implemented in clinical studies. Now, a number of collaborative studies within COG, GPOH, and SIOPEN use genomic information to stratify therapy for patients with localized and metastatic disease. Recently, new types of DNA based aberrations influencing the clinical behavior of neuroblastomas have been described. Deletions or mutations of genes like ATRX and a phenomenon referred to as "chromothripsis" are all assumed to correlate with an unfavorable clinical behavior. However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques. Single nucleotide polymorphism arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine. Here, we present an ultra-high density (UHD) SNParray technique which is, because of its high specificity and sensitivity and the combined copy number and allele information, highly appropriate for the genomic diagnosis of neuroblastoma and other malignancies.

No MeSH data available.


Related in: MedlinePlus

A detailed view of the genomic features of the chromothripsis case described in Figure 7. The chromothripsis with 60 breakpoints lying in both chromosomal arms (chromosome 2) lead to a large number of copy number variations represented in an oscillating copy number profile (visible in all tracks). In addition, the profile shows two amplicons including MYCN and ALK besides other genes (highlighted by asterisks).
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Figure 8: A detailed view of the genomic features of the chromothripsis case described in Figure 7. The chromothripsis with 60 breakpoints lying in both chromosomal arms (chromosome 2) lead to a large number of copy number variations represented in an oscillating copy number profile (visible in all tracks). In addition, the profile shows two amplicons including MYCN and ALK besides other genes (highlighted by asterisks).

Mentions: Due to the design of a Circos plot, only a condensed form of data can be presented. For detailed analyses, as shown in Figures 3–5 and 8–10 (and Figure S1 in Supplementary Material), SNParray data are given in single chromosome (complete or detail) views. The data in this detailed graphical visualization according to the ChAS software are arranged differently as compared to the Circos plot. The cytoband information at the bottom of the graph is followed by the gene annotations (red bars) in the next track. In this lower field of the detailed view, the software also allows for the visualization of information which is not shown in this presentation. Most importantly, the copy number variations (CNVs) with the corresponding annotations can be shown for every genomic locus, thus helping to better interpret microdeletions and -gains (Figure S1 in Supplementary Material). The next track in Figures 3–5, 8 and 10, represented by a line, indicates the so called “smooth signal” – the underlying algorithm performs a smoothing of the copy number information thus providing helpful, albeit sometimes crude, information on the copy number state of the chromosome or parts thereof. This information in combination with the log2 information and, importantly, together with the allele frequency data, allows a detailed identification of the underlying genomic changes.


Ultra-High Density SNParray in Neuroblastoma Molecular Diagnostics.

Ambros IM, Brunner C, Abbasi R, Frech C, Ambros PF - Front Oncol (2014)

A detailed view of the genomic features of the chromothripsis case described in Figure 7. The chromothripsis with 60 breakpoints lying in both chromosomal arms (chromosome 2) lead to a large number of copy number variations represented in an oscillating copy number profile (visible in all tracks). In addition, the profile shows two amplicons including MYCN and ALK besides other genes (highlighted by asterisks).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129917&req=5

Figure 8: A detailed view of the genomic features of the chromothripsis case described in Figure 7. The chromothripsis with 60 breakpoints lying in both chromosomal arms (chromosome 2) lead to a large number of copy number variations represented in an oscillating copy number profile (visible in all tracks). In addition, the profile shows two amplicons including MYCN and ALK besides other genes (highlighted by asterisks).
Mentions: Due to the design of a Circos plot, only a condensed form of data can be presented. For detailed analyses, as shown in Figures 3–5 and 8–10 (and Figure S1 in Supplementary Material), SNParray data are given in single chromosome (complete or detail) views. The data in this detailed graphical visualization according to the ChAS software are arranged differently as compared to the Circos plot. The cytoband information at the bottom of the graph is followed by the gene annotations (red bars) in the next track. In this lower field of the detailed view, the software also allows for the visualization of information which is not shown in this presentation. Most importantly, the copy number variations (CNVs) with the corresponding annotations can be shown for every genomic locus, thus helping to better interpret microdeletions and -gains (Figure S1 in Supplementary Material). The next track in Figures 3–5, 8 and 10, represented by a line, indicates the so called “smooth signal” – the underlying algorithm performs a smoothing of the copy number information thus providing helpful, albeit sometimes crude, information on the copy number state of the chromosome or parts thereof. This information in combination with the log2 information and, importantly, together with the allele frequency data, allows a detailed identification of the underlying genomic changes.

Bottom Line: However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses.However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques.Single nucleotide polymorphism arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine.

View Article: PubMed Central - PubMed

Affiliation: Children's Cancer Research Institute, St. Anna Kinderkrebsforschung , Vienna , Austria.

ABSTRACT
Neuroblastoma serves as a paradigm for applying tumor genomic data for determining patient prognosis and thus for treatment allocation. MYCN status, i.e., amplified vs. non-amplified, was one of the very first biomarkers in oncology to discriminate aggressive from less aggressive or even favorable clinical courses of neuroblastoma. However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses. So called "segmental chromosomal aberrations," (SCAs) i.e., gains or losses of chromosomal fragments, can also indicate tumor aggressiveness. The clinical use of these genomic aberrations has, however, been hampered for many years by methodical and interpretational problems. Only after reaching worldwide consensus on markers, methodology, and data interpretation, information on SCAs has recently been implemented in clinical studies. Now, a number of collaborative studies within COG, GPOH, and SIOPEN use genomic information to stratify therapy for patients with localized and metastatic disease. Recently, new types of DNA based aberrations influencing the clinical behavior of neuroblastomas have been described. Deletions or mutations of genes like ATRX and a phenomenon referred to as "chromothripsis" are all assumed to correlate with an unfavorable clinical behavior. However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques. Single nucleotide polymorphism arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine. Here, we present an ultra-high density (UHD) SNParray technique which is, because of its high specificity and sensitivity and the combined copy number and allele information, highly appropriate for the genomic diagnosis of neuroblastoma and other malignancies.

No MeSH data available.


Related in: MedlinePlus