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Article Dans Une Revue British Journal of Cancer Année : 2007

Identification of genetic alterations in pancreatic cancer by the combined use of tissue microdissection and array-based comparative genomic hybridisation

T Harada
  • Fonction : Auteur
P Baril
R Gangeswaran
  • Fonction : Auteur
G Kelly
  • Fonction : Auteur
V Bhakta
  • Fonction : Auteur
K Caulee
  • Fonction : Auteur
Pc Mahon
  • Fonction : Auteur
Nr Lemoine
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-02086372 , version 1 (01-04-2019)

Identifiants

Citer

T Harada, P Baril, R Gangeswaran, G Kelly, C. Chelala, et al.. Identification of genetic alterations in pancreatic cancer by the combined use of tissue microdissection and array-based comparative genomic hybridisation. British Journal of Cancer, 2007, 96 (2), pp.373-382. ⟨10.1038/sj.bjc.6603563⟩. ⟨hal-02086372⟩
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