Abstract
To identify genomic abnormalities characteristic of pancreatic ductal adenocarcinoma (PDAC) in vivo, a panel of 27 microdissected PDAC specimens were analysed using high-density microarrays representing ∼116 000 single nucleotide polymorphism (SNP) loci. We detected frequent gains of 1q, 2, 3, 5, 7p, 8q, 11, 14q and 17q (⩾78% of cases), and losses of 1p, 3p, 6, 9p, 13q, 14q, 17p and 18q (⩾44%). Although the results were comparable with those from array CGH, regions of those genetic changes were defined more accurately by SNP arrays. Integrating the Ensembl public data, we have generated ‘gene’ copy number indices that facilitate the search for novel candidates involved in pancreatic carcinogenesis. Copy numbers in a subset of the genes were validated using quantitative real-time PCR. The SKAP2/SCAP2 gene (7p15.2), which belongs to the src family kinases, was most frequently (63%) amplified in our sample set and its recurrent overexpression (67%) was confirmed by reverse transcription–PCR. Furthermore, fluorescence in situ hybridization and in situ RNA hybridization analyses for this gene have demonstrated a significant correlation between DNA copy number and mRNA expression level in an independent sample set (P<0.001). These findings indicate that the dysregulation of SKAP2/SCAP2, which is mostly caused by its increased gene copy number, is likely to be associated with the development of PDAC.
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Abbreviations
- array CGH:
-
array-based comparative genomic hybridization
- DCN:
-
DNA copy number
- FISH:
-
fluorescence in situ hybridization
- ISH:
-
in situ RNA hybridization
- LOH:
-
loss of heterozygosity
- PDAC:
-
pancreatic ductal adenocarcinoma
- q-PCR:
-
quantitative real-time PCR
- RT–PCR:
-
reverse transcription–PCR
- SNP:
-
single nucleotide polymorphism
- UPD:
-
uniparental disomy
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Acknowledgements
This work was supported by Cancer Research UK (C355/A6254). We thank Professor Kiwamu Okita (Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine) for providing clinical samples of PDAC.
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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).
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Harada, T., Chelala, C., Bhakta, V. et al. Genome-wide DNA copy number analysis in pancreatic cancer using high-density single nucleotide polymorphism arrays. Oncogene 27, 1951–1960 (2008). https://doi.org/10.1038/sj.onc.1210832
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DOI: https://doi.org/10.1038/sj.onc.1210832
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