Identification of frequent chromosomal aberrations in ductal adenocarcinoma of the pancreas by comparative genomic hybridization (CGH)

Schleger, Christiane; Arens, Norbert; Zentgraf, Hanswalter; Bleyl, U.; Verbeke, Caroline S.

doi:10.1002/(sici)1096-9896(200005)191:1<27::aid-path582>3.0.co;2-j

Cited by 72 publications

(31 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The deregulation of RelA might be caused by altered intracellular signal transduction or chromosomal overrepresentation of the respective gene locus. And in fact RELA amplification has been described in various solid tumours (Rayet and Gelinas, 1999), but not in ductal pancreatic adenocarcinomas (Schleger et al, 2000).…”

Section: Shuklamentioning

confidence: 98%

High expression of RelA/p65 is associated with activation of nuclear factor-κB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

et al. 2007

View full text Add to dashboard Cite

Activation of nuclear factor-kB (NF-kB) signaling was observed in pancreatic adenocarcinoma cell lines and tumours. However, information on the expression of RelA/p65, the major transcription activating NF-kB subunit, in these carcinomas and possible correlations thereof with NF-kB activation and patient survival is not available. To provide this missing translational link, we analysed expression of RelA/p65 in 82 pancreatic adenocarcinomas by immunohistochemistry. Moreover, we measured activation of the NF-kB pathway in 11 tumours by quantitative PCR for NF-kB target genes. We observed strong cytoplasmic or nuclear expression of RelA/p65 in 42 and 37 carcinomas, respectively. High cytoplasmic and nuclear expression of RelA/p65 had negative prognostic impact with 2-year survival rates for patients without cytoplasmic or nuclear RelA/p65 positivity of 41 and 40% and rates for patients with strong cytoplasmic or nuclear RelA/p65 expression of 22 and 20%, respectively. High RelA/p65 expression was correlated to increased expression of NF-kB target genes. The observation that high expression of RelA/p65 is correlated to an activation of the NF-kB pathway and indicates poor patient survival identifies a patient subgroup that might particularly benefit from NF-kB-inhibiting agents in the treatment of pancreatic cancer. Based on our findings, this subgroup could be identified by applying simple immunohistochemical techniques.

show abstract

Section: Shuklamentioning

confidence: 98%

High expression of RelA/p65 is associated with activation of nuclear factor-κB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Previous cytogenetic studies have shown that chromosome arms 7p and 18q may include oncogenes and tumour suppressor genes that play a critical role in pancreatic carcinogenesis (Griffin et al, 1995;Hahn et al, 1995;Fukushige et al, 1997Fukushige et al, , 1998Mahlamaki et al, 1997;Schleger et al, 2000;Harada et al, 2002a;IacobuzioDonahue et al, 2004). Therefore, we prioritised three regions (7p22.3 -p15.1, 18q12.3 -q21.2 and 18q21.2 -q22.1) of nonrandom copy number changes detected in array CGH and a subset of four BAC clones (RP11-403N12 at 7p21.1, RP11-232C20 at 7p15.2, RP11-8H2 at 18q21.1 and RP11-350K6 at 18q21.32) were selected from those regions ( Table 3).…”

Section: Verification Of Genetic Changes By Two-colour Fishmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

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 (43.0 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.

show abstract

“…They also found that 47% of human gastric cancer cell lines lost expression of RUNX3 through a combination of hemizygous deletion of 1p36 and methylation of the RUNX3 promoter region (Li et al, 2002). Interestingly, 1p36, where RUNX3 maps to (Bae et al, 1995), is a region commonly deleted in a wide variety of human carcinomas, including those of the bile duct and pancreas (Weith et al, 1996;Kang et al, 2000;Schleger et al, 2000). In the present study, therefore, to elucidate the roles of RUNX3 in carcinogenesis of the bile duct and pancreas, we examined not only the expression but also the methylation status of RUNX3 in human bile duct and pancreatic cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines

et al. 2004

View full text Add to dashboard Cite

RUNX3, a Runt domain transcription factor involved in TGF-b signaling, is a candidate tumor-suppressor gene localized in 1p36, a region commonly deleted in a wide variety of human tumors, including those of the stomach, bile duct, and pancreas. Recently, frequent inactivation of RUNX3 has been demonstrated in human gastric carcinomas. In this study, to examine the involvement of RUNX3 abnormalities in tumorigenesis of bile duct as well as pancreatic cancers, we investigated not only the expression but also methylation status of RUNX3 in 10 human bile duct and 12 pancreatic cancer cell lines. Seven (70%) of the bile duct and nine (75%) of the pancreatic cancer cell lines exhibited no expression of RUNX3 by both Northern blot analysis and the reverse transcriptase polymerase chain reaction. All of the 16 cell lines that did not express RUNX3 also showed methylation of the promoter CpG island of the gene, whereas the six cell lines that showed RUNX3 expression were not methylated or only partially methylated in the RUNX3 promoter region. Moreover, treatment with the methylation inhibitor 5 0 -aza-2 0 -deoxycitidine activated RUNX3 mRNA expression in all of 16 cancer cell lines that originally lacked RUNX3 expression. Finally, hemizygous deletion of RUNX3, as detected by fluorescence in situ hybridization, was found in 15 of the 16 cancer cell lines that lacked RUNX3 expression. These data suggest that the inactivation of RUNX3 plays an important role in bile duct and pancreatic carcinogenesis, and that methylation is a common mechanism by which the gene is inactivated.

show abstract

Identification of frequent chromosomal aberrations in ductal adenocarcinoma of the pancreas by comparative genomic hybridization (CGH)

Cited by 72 publications

References 17 publications

High expression of RelA/p65 is associated with activation of nuclear factor-κB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

High expression of RelA/p65 is associated with activation of nuclear factor-κB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

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

Frequent loss of RUNX3 gene expression in human bile duct and pancreatic cancer cell lines

Contact Info

Product

Resources

About