Limits...
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

The log2 copy number plot displays the structural variations in the ATRX gene. (A) Complete chromosome X with small deletion at Xq21.1 visible in the zoomed-in chromosomal sub-band. The dots indicate the log2 copy values of individual copy number probes. The intron–exon structure of ATRX is shown in red (vertical bars are exons). (B) Five examples of ATRX deletions spanning different parts of the gene are depicted (log2 ratio from five neuroblastomas are shown in different colors analyzed with the ChAS software).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4129917&req=5

Figure 9: The log2 copy number plot displays the structural variations in the ATRX gene. (A) Complete chromosome X with small deletion at Xq21.1 visible in the zoomed-in chromosomal sub-band. The dots indicate the log2 copy values of individual copy number probes. The intron–exon structure of ATRX is shown in red (vertical bars are exons). (B) Five examples of ATRX deletions spanning different parts of the gene are depicted (log2 ratio from five neuroblastomas are shown in different colors analyzed with the ChAS software).

Mentions: Figure 9 shows the X chromosome with a close up highlighting the ATRX gene located in the cytoband Xq21.1. In the upper part of the Figure 9, the copy number probes show a clear deletion spanning from exon 2 to exon 8. In the lower part of the figure, five examples of ATRX gene deletions are given. Among the 213 evaluable samples analyzed in this study, an intragenic deletion of the ATRX gene was found in 21 tumors (9.9%). All ATRX deleted tumors also showed the ALT phenotype (alternative lengthening of telomeres) that is typical for the loss of the ATRX gene function (data not shown).


Ultra-High Density SNParray in Neuroblastoma Molecular Diagnostics.

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

The log2 copy number plot displays the structural variations in the ATRX gene. (A) Complete chromosome X with small deletion at Xq21.1 visible in the zoomed-in chromosomal sub-band. The dots indicate the log2 copy values of individual copy number probes. The intron–exon structure of ATRX is shown in red (vertical bars are exons). (B) Five examples of ATRX deletions spanning different parts of the gene are depicted (log2 ratio from five neuroblastomas are shown in different colors analyzed with the ChAS software).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: The log2 copy number plot displays the structural variations in the ATRX gene. (A) Complete chromosome X with small deletion at Xq21.1 visible in the zoomed-in chromosomal sub-band. The dots indicate the log2 copy values of individual copy number probes. The intron–exon structure of ATRX is shown in red (vertical bars are exons). (B) Five examples of ATRX deletions spanning different parts of the gene are depicted (log2 ratio from five neuroblastomas are shown in different colors analyzed with the ChAS software).
Mentions: Figure 9 shows the X chromosome with a close up highlighting the ATRX gene located in the cytoband Xq21.1. In the upper part of the Figure 9, the copy number probes show a clear deletion spanning from exon 2 to exon 8. In the lower part of the figure, five examples of ATRX gene deletions are given. Among the 213 evaluable samples analyzed in this study, an intragenic deletion of the ATRX gene was found in 21 tumors (9.9%). All ATRX deleted tumors also showed the ALT phenotype (alternative lengthening of telomeres) that is typical for the loss of the ATRX gene function (data not shown).

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