Single nucleotide polymorphism array analysis of cancer

Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge 02142, USA.
Current Opinion in Oncology (Impact Factor: 4.47). 02/2007; 19(1):43-9. DOI: 10.1097/CCO.0b013e328011a8c1
Source: PubMed


Classifying tumors and identifying therapeutic targets requires a description of the genetic changes underlying cancer. Single nucleotide polymorphism (SNP) arrays provide a high-resolution platform for describing several types of genetic changes simultaneously. With the resolution of these arrays increasing exponentially, they are becoming increasingly powerful tools for describing the genetic events underlying cancer.
The ability to map loss of heterozygosity (LOH) and overall copy number variations using SNP arrays is known. Techniques have recently been developed to map LOH at high resolution in the absence of paired normal data. Copy number variations described by SNP array studies are now reaching resolutions enabling the identification of novel oncogenes and tumor suppressor genes. The ability to determine allele-specific copy number changes has only recently been described. Moreover, SNP arrays offer a high-throughput platform for large-scale association studies that are likely to lead to the identification of multiple germline variants that predispose to cancer.
SNP arrays are an ideal platform for identifying both somatic and germline genetic variants that lead to cancer. They provide a basis for DNA-based cancer classification and help to define the genes being modulated, improving understanding of cancer genesis and potential therapeutic targets.

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    • "More than a decade into the post-genomic era, we have come to appreciate human malignancy as a condition derived from somatic aberrations in the human genome. Early studies enabled by oligonucleotide hybridization arrays proved to be highly informative, demonstrating a role for somatic copy number variations (CNVs)1, mutations2, and differential transcript expression3 as cancer promoting events. Current efforts build from these successes while benefiting from the rapid evolution of high throughput sequencing and bioinformatics techniques4. "
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    ABSTRACT: Cancer genomics is a rapidly growing discipline in which the genetic molecular basis of malignancy is studied at the scale of whole genomes. While the discipline has been successful with respect to identifying specific oncogenes and tumor suppressors involved in oncogenesis, it is also challenging our approach to managing patients suffering from this deadly disease. Specifically cancer genomics is driving clinical oncology to take a more molecular approach to diagnosis, prognostication, and treatment selection. We review here recent work undertaken in cancer genomics with an emphasis on translation of genomic findings. Finally, we discuss scientific challenges and research opportunities emerging from findings derived through analysis of tumors with high-depth sequencing.
    Cancer Biology and Medicine 12/2013; 10(4):214-220. DOI:10.7497/j.issn.2095-3941.2013.04.005
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    • "The detection of point mutation or single nucleotide polymorphism (SNP) is essential in many fields of biomedical research such as molecular diagnosis, personalized therapy, and drug development (1-3). In the last decades, the detection of rare mutation of cancer genes in the circulating free DNA (cfDNA) of patient’s blood has attracted increasing attention for its potential in tumor diagnosis and personalized treatment (4-7). "
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    ABSTRACT: It is essential to analyze rare mutations in many fields of biomedical research. However, the detection of rare mutations is usually failed due to the interference of predominant wild-type DNA surrounded. Herein we describe a sensitive and facile method of detecting rare point mutation on the basis of allele-specific amplification in emulsion PCR. The identification and selective amplification of rare mutation are accomplished in one-pot reaction. The allele-specific primers coupled on magnetic beads allow the exclusive amplification and enrichment of the mutant amplicons. The productive beads bearing mutant amplicons are subsequently stained with the fluorescent dyes. Thus, the rare point mutations with a percentage as low as 0.1%, can be detected by fluorescent analysis. The relative percentages of mutation among different samples can be roughly accessed by counting the fraction of fluorescent positive beads through flow cytometry. [BMB Reports 2013; 46(5): 270-275].
    BMB reports 05/2013; 46(5):270-275. DOI:10.5483/BMBRep.2013.46.5.155 · 2.60 Impact Factor
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    • "By merging these two analyses, it is possible to identify copy neutral LOH (cnLOH, or uniparental disomy, UPD), a chromosomal defect which comprises 50-70% of all LOH events detected in human tumors [36]. Furthermore, recent high resolution SNP array platforms can identify amplifications/deletions at a single gene level, offering a powerful method for oncogene and tumor suppressor gene discovery [37,38,39]. Recently, we applied this method to investigate the genetic events in a group of 15 benign cortisol-secreting tumors, detecting several recurrent CN gains and losses, mostly microalterations, in both already known and newly identified chromosomal regions. "
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    ABSTRACT: Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs >100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91% vs 29%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr 1, 2, 13, 17, and 22) was associated with a better prognosis (overall survival: 72.2 vs 35.4 months, P=0.063). Interestingly, >70% of gains frequent in beningn were also present in malignant tumors. Notch signaling was the most frequently involved pathway in both tumor entities. Finally, a CN gain at imprinted "IGF2" locus chr 11p15.5 appeared to be an early alteration in a multi-step tumor progression, followed by the loss of one or two alleles, associated with increased IGF2 expression, only in carcinomas. Our study serves as database for the identification of genes and pathways, such as Notch signaling, which could be involved in the pathogenesis of adrenocortical tumors. Using these data, we postulate an adenoma-carcinoma sequence for these tumors.
    PLoS ONE 04/2013; 8(9):e73959. DOI:10.1371/journal.pone.0073959 · 3.23 Impact Factor
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