Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Siân Jones,Xiaosong Zhang,D. Williams Parsons,D. Williams Parsons,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,Hirohiko Kamiyama,Antonio Jimeno,Seung-Mo Hong,Baojin Fu,Ming Tseh Lin,Eric S. Calhoun,Mihoko Kamiyama,Kimberly Walter,Tatiana Nikolskaya,Yuri Nikolsky,James Hartigan,Douglas Smith,Manuel Hidalgo,Steven D. Leach,Alison P. Klein,Elizabeth M. Jaffee,Michael Goggins,Anirban Maitra,Anirban Maitra,Christine A. Iacobuzio-Donahue,James R. Eshleman,Scott E. Kern,Ralph H. Hruban,Rachel Karchin,Nickolas Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +37 more
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TLDR
It is found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations, which defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors.Abstract:
There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. Then, we searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 10(6) single-nucleotide polymorphisms. We found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Our data indicate that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. Dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis.read more
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Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment.
Kishore Polireddy,Qi Chen +1 more
TL;DR: The molecular biology of pancreatic cancer, the major signaling pathways regulating Pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreaticcancer are reviewed.
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miRNAs in pancreatic cancer: therapeutic potential, delivery challenges and strategies.
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Whole-genome sequencing of salivary gland adenoid cystic carcinoma
Eleni M. Rettig,C. Conover Talbot,Mark Sausen,Sian Jones,Justin A. Bishop,Laura D. Wood,Collin Tokheim,Noushin Niknafs,Rachel Karchin,Elana J. Fertig,Sarah J. Wheelan,Luigi Marchionni,Michael Considine,Carole Fakhry,Carole Fakhry,Nickolas Papadopoulos,Kenneth W. Kinzler,Bert Vogelstein,Patrick K. Ha,Patrick K. Ha,Nishant Agrawal,Nishant Agrawal +21 more
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Metabolic tumour burden assessed by 18F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection
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I. Amanam,Vincent Chung +1 more
TL;DR: Progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year, and there is an urgent need for improved therapies with better efficacy and less toxicity.
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