Novel technology for detection of genomic and transcriptional alterations in pancreatic cancer

Wallrapp, Christine; Müller-Pillasch, F.; Micha, Anne E.; Wenger, Christoph; Geng, Michael; Solinas‐Toldo, Sabina; Lichter, Peter; Frohme, Marcus; Hoheisel, Jöerg; Adler, Guido; Gress, Thomas M.

doi:10.1093/annonc/10.suppl_4.s64

Cited by 5 publications

(4 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, there have been many studies describing the expression profiles of normal pancreas, CP, and PDAC samples; [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]50 however, the analysis of PanINs has been hampered by the difficulty of obtaining sufficient material and number of these samples. Not all PanINs progress to malignant disease and it is hoped that analysis of these precursor lesions will result in the identification of genes that can be used to determine high-risk PanINs, ie, those likely to progress to invasive PDAC.…”

Section: Discussionmentioning

confidence: 99%

“…14 -16 Recent studies using Affymetrix and cDNA microarrays have identified a number of differentially expressed genes in PDAC. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Among these genes S100P has been identified as a potential biomarker for pancreatic adenocarcinoma, being highly up-regulated in pancreatic tumors and cell lines. 20,[23][24][25][26]31,32 S100P is a member of the S100 family of EF-hand, calcium-binding proteins.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Expression of S100P and Its Novel Binding Partner S100PBPR in Early Pancreatic Cancer

Dowen

Crnogorac‐Jurčević

Gangeswaran

et al. 2005

The American Journal of Pathology

117

View full text Add to dashboard Cite

S100P is a member of the S100 family of calcium-binding proteins and there have been several recent reports of its overexpression in pancreatic ductal adenocarcinoma (PDAC). We have used Far Western screening and in vitro interaction assays to identify and confirm a novel target protein for S100P. We have named this protein S100PBPR, and shown that its interaction with S100P is dependent on Ca(2+) or Mg(2+). S100PBPR was found to localize to cell nuclei where S100P is also present, and the two proteins co-immunoprecipitate. By in situ hybridization, S100PBPR transcript was found in islet cells but not duct cells of the healthy pancreas. Both S100P and S100PBPR were detected by quantitative real-time polymerase chain reaction in pancreatic intraepithelial neoplasia (PanIN) and PDAC samples, and in situ hybridization revealed the presence of S100PBPR transcript in malignant PDAC cells. These data suggest that an interaction between S100P and S100PBPR may be involved in early pancreatic cancer. S100P was further investigated in PanIN lesions and immunohistochemical analysis showed its expression to correlate significantly with increasing grade of PanINs, being found as early as PanIN-1 with more prevalent expression in PanIN-2 and -3. These data suggest that S100P can be added to the genetic progression model for PDAC.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Expression of S100P and Its Novel Binding Partner S100PBPR in Early Pancreatic Cancer

Dowen

Crnogorac‐Jurčević

Gangeswaran

et al. 2005

The American Journal of Pathology

117

View full text Add to dashboard Cite

show abstract

“…Compared to only 5 years ago, we are now aware of hundreds of genes with potential importance in the biology of pancreatic cancer. 6 -11 Strategies for identifying differentially expressed genes in pancreatic cancer have progressed from initial studies using gridded cDNA libraries, 12 and later representational difference analysis of cDNAs, 7,9,13 to the newer strategies of serial analysis of gene expression, 14,15 oligonucleotide microarrays, 11 and cDNA microarrays. 8 To differentiate gene expression patterns arising from the pri-mary cancer from those arising in the surrounding stroma investigators have used several strategies including limiting their analysis to comparison of pancreatic cancer cell lines with normal pancreas, 8 comparing pancreatic cancer cell lines with normal pancreatic ductal epithelium, 15 whereas other investigators have used laser capture microdissection.…”

Section: Ity Of Pancreatic Cancers Analyzed the Genes And Expressed mentioning

confidence: 99%

Exploration of Global Gene Expression Patterns in Pancreatic Adenocarcinoma Using cDNA Microarrays

Iacobuzio‐Donahue

Maitra

Olsen

et al. 2003

The American Journal of Pathology

433

284

View full text Add to dashboard Cite

Pancreatic cancer is the fifth leading cause of cancer death in the United States. We used cDNA microarrays to analyze global gene expression patterns in 14 pancreatic cancer cell lines, 17 resected infiltrating pancreatic cancer tissues, and 5 samples of normal pancreas to identify genes that are differentially expressed in pancreatic cancer. We found more than 400 cDNAs corresponding to genes that were differentially expressed in the pancreatic cancer tissues and cell lines as compared to normal pancreas. These genes that tended to be expressed at higher levels in pancreatic cancers were associated with a variety of processes, including cell-cell and cell-matrix interactions, cytoskeletal remodeling, proteolytic activity, and Ca(++) homeostasis. Two prominent clusters of genes were related to the high rates of cellular proliferation in pancreatic cancer cell lines and the host desmoplastic response in the resected pancreatic cancer tissues. Of 149 genes identified as more highly expressed in the pancreatic cancers compared with normal pancreas, 103 genes have not been previously reported in association with pancreatic cancer. The expression patterns of 14 of these highly expressed genes were validated by either immunohistochemistry or reverse transcriptase-polymerase chain reaction as being expressed in pancreatic cancer. The overexpression of one gene in particular, 14-3-3 sigma, was found to be associated with aberrant hypomethylation in the majority of pancreatic cancers analyzed. The genes and expressed sequence tags presented in this study provide clues to the pathobiology of pancreatic cancer and implicate a large number of potentially new molecular markers for the detection and treatment of pancreatic cancer.

show abstract

“…21,[70][71][72][73][74] Some robust patterns are seen. A primary tumor's gene expression pattern is the overlay of at least six discernable tissue types: the neoplastic cells, the angioendothelial structures, the juxtatumoral stroma, the panstromal compartment, the leukocytic infiltrate, and the invaded and incorporated remaining parenchymal cells.…”

Section: Does Pancreatic Cancer Have Distinctive Gene Expression Pattmentioning

confidence: 99%

An Introduction to Pancreatic Adenocarcinoma Genetics, Pathology and Therapy

Kern

Hruban²,

Hidalgo³

et al. 2002

Cancer Biology & Therapy

View full text Add to dashboard Cite

Cancer is bad, but pancreatic cancer is especially so. Underlying the aggressive behavior of pancreatic cancer is a highly patterned set of biologic rules for its development. The accumulating discoveries regarding the genetic basis of pancreatic cancer and developments in the clinical management of the disease provide hope for meaningful improvements in the understanding and control of this disease. WHAT IS A TYPICAL PRESENTATION FOR THIS DISEASE?Pancreatic cancer is usually diagnosed at a biologically late stage. A patient, usually in their 60s or 70s, may notice unexplained weight loss, back pain, altered bowel habits, or the sudden onset of jaundice. During the clinical evaluation, a mass is found in the pancreas, usually in the head, the right-sided region of pancreas adjacent to the duodenum. Unfortunately, in 80% of these patients it is clinically evident that the cancer has already spread to other organs, most commonly in the liver. The only options for these patients include palliation (procedures such as placement of a stent within an occluded biliary duct) or noncurative courses of chemotherapy. A subset of patients, about 20%, will, however, have no detectable metastatic disease. These patients are candidates for a surgical resection.Pancreatic adenocarcinoma affects close to 30,000 persons a year in the United States and is the fourth most common form of cancer death in both sexes. WHAT ARE THE SURGICAL OPTIONS?For patients with tumors in the head of the gland, options for resection include a pancreaticoduodenectomy (or Whipple operation). A minority of patients will have tumors originating in the left side, or tail, of the gland, and are candidates for distal pancreatectomy, usually with splenectomy. The five-year survival for the groups of patients who do not undergo resectional procedures is clearly less than five percent. In the group of patients who undergo surgical resection, five-year survival rates are largely between 15 and 20%. 1 Within this latter group, patients with small cancers, cancer-free margins of resection, and without metastases to local lymph nodes will be expected to have an even better prognosis approaching 40% five-year survival overall. Nearly all patients who undergo surgical resection, unfortunately, eventually succumb to metastatic disease, including even the cases resected when the primary lesion is extremely small. 2,3 The implication is that pancreatic cancer must metastasize distantly, prior to clinical presentation, in virtually all cases. WHERE SHOULD PANCREATIC CANCER SURGERY BE DONE?Considerable data would support the centralization of pancreatic cancer surgery to specific "centers of excellence". The first such analyses came from the state of Maryland and compared cost and outcome between one high-volume regional provider and 38 other Maryland hospitals during a five-year period. 4 Hospital mortality was six times higher for patients treated at low-volume providers; mortality rates specifically increased with decreasing volume, from 2.2% at the regional ...

show abstract

Novel technology for detection of genomic and transcriptional alterations in pancreatic cancer

Cited by 5 publications

References 24 publications

Expression of S100P and Its Novel Binding Partner S100PBPR in Early Pancreatic Cancer

Expression of S100P and Its Novel Binding Partner S100PBPR in Early Pancreatic Cancer

Exploration of Global Gene Expression Patterns in Pancreatic Adenocarcinoma Using cDNA Microarrays

An Introduction to Pancreatic Adenocarcinoma Genetics, Pathology and Therapy

Contact Info

Product

Resources

About