Genotyping techniques to address diversity in tumors.
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Citations
Heterogeneous Challenges for Urologic Cancers
DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation
Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship.
Iam hiQ—a novel pair of accuracy indices for imputed genotypes
Genome-wide profiling of copy number alterations in cancer: focus on melanoma
References
Hallmarks of cancer: the next generation.
Quantitative monitoring of gene expression patterns with a complementary DNA microarray.
Comparative Genomic Hybridization for Molecular Cytogenetic Analysis of Solid Tumors
Detection of large-scale variation in the human genome.
Large-Scale Copy Number Polymorphism in the Human Genome
Related Papers (5)
SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution.
Frequently Asked Questions (14)
Q2. Why do the authors refrain from using the term UPD when discussing copy number neutral imbalance events?
Due to its narrow definition – homozygosity caused by two copies from the same parent – and close association with constitutional genetics, the authors will refrain from using the term UPD when discussing copy number neutral allelic imbalance events.
Q3. What are the main uses of LOH analysis?
LOH analyses have, on the other hand, been widely used in cancer research to detect regions of allelic imbalances indicating regions of genomic deletion or copy number neutral LOH, and have been used to identify tumor suppressor genes inactivated by mutation followed by loss of the wild-type allele.
Q4. What makes SNP arrays ideal for the identification of copy number neutral imbalances?
The combination of genotype and copy number measurements makes SNP arrays ideal for the identification of copy number neutral imbalances.
Q5. How many bands are possible for a normal genome?
The BAF profile of a homozygous genome, e.g., a haploid genome, will consequently present only 2 bands, restricted to theoretical BAF values 0 and 1, whereas a triploid genome will show four bands.
Q6. What technology is used to immobilize probes?
Illumina utilizes their BeadChip technology that permits probes to be immobilized on silica beads rather than directly onto the array surface.
Q7. What can be done to reduce the complexity of data?
Although values from individual SNPs can be plotted, various segmentation approaches can effectively reduce the complexity of data, i.e., defining regions of genomic balance or imbalance and treating these as individual events assigned representative mBAF and LRR values.
Q8. How can the authors calculate BAF values for heterogeneous samples?
Equation (1) can with some minor modifications be used to calculate BAFvalues for any given locus in case of heterogeneous samples.
Q9. What are the main advantages of SNP arrays?
SNP array platforms have also successfully been applied to address problems regarding intermixture of nonaberrant cell populations.
Q10. What is the significance of the interplay between cells within the tumor microenvironment?
The interplay between cells within the tumor microenvironment has been highlighted as important hallmarks of cancer and its composition has been shown to represent an intrinsic property of tumors (Hanahan and Weinberg, 2011).
Q11. What is the purpose of the transformation of allele intensities to relative copy number estimates?
Transformation of intensities to relative copy number estimates is essentially also performed by relating values to a collection of normal reference samples (HapMap) or to a matched control.
Q12. How can one circumvent the limited availability of multiple samples from individual patients?
The limited availability of multiple samples from individual patients can be circumvented by macro or micro dissection (Navin et al., 2010) or cell sorting procedures followed by expansion in animal models (Navin et al., 2011), effectively performing multiple samplings of the same tumor.
Q13. What is the expected BAF and LRR for a normal genome?
Examples of expected BAF and LRR values for a normal genome and how these values are affected by acquired genetic aberrations is further discussed below.D. Expected BAF and LRR for a Normal GenomeIn a diploid genome, there are only three possible allele combinations for agiven locus: homozygosity for the A allele (AA), heterozygosity (AB) orhomozygosity for the B allele (BB).
Q14. How many bands are seen when analyzing a normal diploid genome?
The authors previously described that, when considering a larger series of SNPs, a BAF plot will appear as banded and that three bands are seen when analyzing a normal diploid genome.