Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Application of SNP microarrays to the genome-wide analysis of chromosomal instability in premalignant airway lesions

ABSTRACT: Chromosomal instability is central to the process of carcinogenesis. The detection of somatic chromosomal alterations in small premalignant lesions genome-wide remains challenging since sample heterogeneity dilutes the aberrant cell information. We introduced an analytic metric termed "delta-θ", and applied this metric to a titrated cancer cell model using a pair of cancer cell line and matched lymphoblastoid cell line. We examined heterogeneous clinical specimens including bronchial biopsies and brushings with this metric. Distinctive genomic variation were successfully detected across the whole genome in invasive cancer cases (6/6), carcinoma in situ (3/3), and high grade dysplasia (severe or moderate) (3/11). We modeled titration series (100%, 25%, 12.5%, 6.3%, 3.1%, 1.6% and 0% tumor content) mixing the genomic DNA of the cell line pair. We also investigated 30 malignant/premalignant samples from 18 patients with heavy smoking histories (6 invasive lung cancer, 3 carcinoma in situ,15 dysplasia, 3 hyperplasia and 3 normal histology) using Illumina HumanOmni2.5 and Human 660w SNP microarrays. All of them were paired with matched reference blood DNA and analyzed.

ORGANISM(S): Homo sapiens

SUBMITTER: Ichiro Nakachi

PROVIDER: E-GEOD-43168 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Application of SNP microarrays to the genome-wide analysis of chromosomal instability in premalignant airway lesions.

Nakachi Ichiro I Rice Jessica L JL Coldren Christopher D CD Edwards Michael G MG Stearman Robert S RS Glidewell Steven C SC Varella-Garcia Marileila M Franklin Wilbur A WA Keith Robert L RL Lewis Marina T MT Gao Bifeng B Merrick Daniel T DT Miller York E YE Geraci Mark W MW

Cancer prevention research (Philadelphia, Pa.) 20131217 2

Chromosomal instability is central to the process of carcinogenesis. The genome-wide detection of somatic chromosomal alterations (SCA) in small premalignant lesions remains challenging because sample heterogeneity dilutes the aberrant cell information. To overcome this hurdle, we focused on the B allele frequency data from single-nucleotide polymorphism microarrays (SNP arrays). The difference of allelic fractions between paired tumor and normal samples from the same patient (delta-θ) provides ...[more]

PMID: 24346345

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Project description:In colorectal cancer (CRC), chromosomal instability (CIN) is typically studied using comparative-genomic hybridization (CGH) arrays. We studied paired (tumor and surrounding healthy) fresh-frozen tissue from 86 CRC patients using Illumina’s Infinium-based SNP array. This method allowed us to study CIN in CRC, with simultaneous analysis of copy number (CN) and B-allele frequency (BAF), which is a representation of allelic composition. This data helped us to detect mono-allelic and bi-allelic amplifications/deletion, copy neutral loss of heterozygosity, and levels of mosaicism for mixed cell populations, some of which can not be assessed with other methods that do not measure BAF. We identified associations between CN abnormalities and different CRC phenotypes (MSI, histological diagnosis, location, tumor grade, stage, MSI and presence of lymph node metastasis). We showed commonalities between regions of CN change observed in CRC and the regions reported in previous studies of other solid cancers (e.g., amplifications of 20q, 13q, 8q, 5p and deletions of 18q, 17p and 8p). From the Therapeutic Target Database we found relevant drugs, targeted to the genes located in these regions with CN changes, approved or in trials for other cancers and common diseases. These drugs may be considered for future therapeutic trials in CRC, based on personalized cytogenetic diagnosis. We also found many regions harboring genes which are not currently targeted by any relevant drugs that may be considered for future drug discovery studies. Our study shows the application of high-density SNP arrays for cytogenetic study in CRC and its importance for personalized treatment. DNA was extracted from colon tissue samples provided by 86 CRC patients. Each patient provided paired CRC tumor tissue and adjacent normal colon mucosa samples, which were fresh-frozen after resection. Samples were genotyped using Illumina's Infinium-based 610 Quad and CytoSNP 12 microarray chips. The genotype data from paired tumor and normal samples was used to detect tumor-specific chromosomal instabilities in copy number, including copy-neutral LOH, which cannot be assessed by many other cytogenetic methods. Supplementary file "GSE34678_raw_GPL8887.txt" includes the raw data for Samples using GPL8887 (GSM853162-GSM853239); supplementary file "GSE34678_raw_GPL13829.txt" includes the raw data for Samples using GPL13829 (GSM853240-GSM853363).

Dataset Information

Application of SNP microarrays to the genome-wide analysis of chromosomal instability in premalignant airway lesions

Publications

Application of SNP microarrays to the genome-wide analysis of chromosomal instability in premalignant airway lesions.

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