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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

Circos plot showing the normal chromosomal complement from a Schwann cell dominant tumor. The outer ring indicates the chromosome ideograms and distances in Mb. The next ring indicates the copy number information. All autosomes are disomic (black dots), the X and Y chromosomes are present in one copy each (red dots). The innermost ring represents the allele peak frequency of the chromosomes. All autosomes disclose three allele peak tracks whereas the X and Y chromosomes show only two tracks; exception: the pseudo-autosomal regions on the tips of the X chromosome, which have three allele tracks.
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Figure 1: Circos plot showing the normal chromosomal complement from a Schwann cell dominant tumor. The outer ring indicates the chromosome ideograms and distances in Mb. The next ring indicates the copy number information. All autosomes are disomic (black dots), the X and Y chromosomes are present in one copy each (red dots). The innermost ring represents the allele peak frequency of the chromosomes. All autosomes disclose three allele peak tracks whereas the X and Y chromosomes show only two tracks; exception: the pseudo-autosomal regions on the tips of the X chromosome, which have three allele tracks.

Mentions: Although in the daily routine work, the single chromosome genome analysis – as it is done, e.g., by the ChAS software (for details see Materials and Methods section and Supplementary Materials) – is indispensable, we start our introduction into UHD SNP array analysis with a whole genome visualization. One way to present all genomic changes in one graph is to use the so called Circos plots. This type of visualization tool allows the identification of copy number changes at one glance. In the different Circos plots presented in this paper (Figures 1, 2, 6, and 7 and Figure S2 in Supplementary Material), the following information is provided: the chromosome ideograms with the Mb information are located along the outside of the diagram. It is followed inwards by the copy number probe track and the allele frequency track. In case there are whole chromosome/segmental gains or losses, the copy number track is labeled in the usual color code, i.e., blue color indicates gain or amplification of chromosomal material and red indicates loss of material.


Ultra-High Density SNParray in Neuroblastoma Molecular Diagnostics.

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

Circos plot showing the normal chromosomal complement from a Schwann cell dominant tumor. The outer ring indicates the chromosome ideograms and distances in Mb. The next ring indicates the copy number information. All autosomes are disomic (black dots), the X and Y chromosomes are present in one copy each (red dots). The innermost ring represents the allele peak frequency of the chromosomes. All autosomes disclose three allele peak tracks whereas the X and Y chromosomes show only two tracks; exception: the pseudo-autosomal regions on the tips of the X chromosome, which have three allele tracks.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Circos plot showing the normal chromosomal complement from a Schwann cell dominant tumor. The outer ring indicates the chromosome ideograms and distances in Mb. The next ring indicates the copy number information. All autosomes are disomic (black dots), the X and Y chromosomes are present in one copy each (red dots). The innermost ring represents the allele peak frequency of the chromosomes. All autosomes disclose three allele peak tracks whereas the X and Y chromosomes show only two tracks; exception: the pseudo-autosomal regions on the tips of the X chromosome, which have three allele tracks.
Mentions: Although in the daily routine work, the single chromosome genome analysis – as it is done, e.g., by the ChAS software (for details see Materials and Methods section and Supplementary Materials) – is indispensable, we start our introduction into UHD SNP array analysis with a whole genome visualization. One way to present all genomic changes in one graph is to use the so called Circos plots. This type of visualization tool allows the identification of copy number changes at one glance. In the different Circos plots presented in this paper (Figures 1, 2, 6, and 7 and Figure S2 in Supplementary Material), the following information is provided: the chromosome ideograms with the Mb information are located along the outside of the diagram. It is followed inwards by the copy number probe track and the allele frequency track. In case there are whole chromosome/segmental gains or losses, the copy number track is labeled in the usual color code, i.e., blue color indicates gain or amplification of chromosomal material and red indicates loss of material.

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