Journal
BRITISH JOURNAL OF CANCER
Volume 96, Issue 2, Pages 373-382Publisher
SPRINGERNATURE
DOI: 10.1038/sj.bjc.6603563
Keywords
pancreatic cancer; tissue microdissection; array CGH; SEC11L3
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Pancreatic ductal adenocarcinoma (PDAC) is characterised pathologically by a marked desmoplastic stromal reaction that significantly reduces the sensitivity and specificity of cytogenetic analysis. To identify genetic alterations that reflect the characteristics of the tumour in vivo, we screened a total of 23 microdissected PDAC tissue samples using array-based comparative genomic hybridisation (array CGH) with 1 Mb resolution. Highly stringent statistical analysis enabled us to define the regions of nonrandom genomic changes. We detected a total of 41 contiguous regions (> 3.0 Mb) of copy number changes, such as a genetic gain at 7p22.2 - p15.1 (26.0 Mb) and losses at 17p13.3 - p11.2 (13.6 Mb), 18q21.2 - q22.1 (12.0 Mb), 18q22.3 - q23 (7.1 Mb) and 18q12.3 - q21.2 (6.9 Mb). To validate our array CGH results, fluorescence in situ hybridisation was performed using four probes from those regions, showing that these genetic alterations were observed in 37 - 68% of a separate sample set of 19 PDAC cases. In particular, deletion of the SEC11L3 gene (18q21.32) was detected at a very high frequency (13 out of 19 cases; 68%) and in situ RNA hybridisation for this gene demonstrated a significant correlation between deletion and expression levels. It was further confirmed by reverse transcription PCR that SEC11L3 mRNA was downregulated in 16 out of 16 PDAC tissues (100%). In conclusion, the combination of tissue microdissection and array CGH provided a valid data set that represents in vivo genetic changes in PDAC. Our results raise the possibility that the SEC11L3 gene may play a role as a tumour suppressor in this disease.
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