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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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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]

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