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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA
Evgeny Izumchenko,Xiaofei Chang,Mariana Brait,Elana J. Fertig,Luciane T. Kagohara,Atul Bedi,Luigi Marchionni,Nishant Agrawal,Rajani Ravi,Sian Jones,Mohammad O. Hoque,William H. Westra,David Sidransky +12 more
TL;DR: Insight is provided into the heterogeneity of clonal events in the progression of early lung neoplasia and it is demonstrated that these events can be detected even before neoplasms have invaded and acquired malignant potential.
Journal ArticleDOI
Antigen-specific vaccines for cancer treatment.
Maria Tagliamonte,Annacarmen Petrizzo,Maria Lina Tornesello,Franco M. Buonaguro,Luigi Buonaguro +4 more
TL;DR: This review summarizes the current state of cancer vaccines, mainly focusing on antigen-specific approaches, and indicates new and more potent strategies are now available to identify specific tumor-associated antigens for development of cancer vaccine approaches aiming at eliciting targeted anti-tumor cellular responses.
Journal ArticleDOI
Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities
Dinesh K. Singh,Chin-Jen Ku,Chonlarat Wichaidit,Robert J. Steininger,Lani F. Wu,Steven J. Altschuler +5 more
TL;DR: It is found that patterns of heterogeneity could be used to separate the most sensitive and resistant populations to paclitaxel within a set of H460 lung cancer clones and within the NCI‐60 panel of cancer cell lines, but not for a set.
Journal ArticleDOI
Tumour-stroma interactions in pancreatic ductal adenocarcinoma: Rationale and current evidence for new therapeutic strategies
TL;DR: Preclinical data indicate that co-treatment with nab-paclitaxel and gem citabine results in stromal depletion, increased tumour vascularization and intratumoural gemcitabine concentration, and increased tumours regression compared with either agent alone, and Phase I/II study data suggest that a high level of antitumor activity can be achieved with this combination in pancreatic cancer.
Journal ArticleDOI
Integrated proteomic profiling of cell line conditioned media and pancreatic juice for the identification of pancreatic cancer biomarkers
Shalini Makawita,Christopher R. Smith,Ihor Batruch,Yingye Zheng,Felix Rückert,Robert Grützmann,Christian Pilarsky,Steven Gallinger,Eleftherios P. Diamandis,Eleftherios P. Diamandis,Eleftherios P. Diamandis +10 more
TL;DR: The combined mining of pancreatic cancer-related cell line conditioned media and pancreatic juice for identification of putative diagnostic leads and preliminary verification of anterior gradient homolog 2, syncollin, olfactomedin-4, polymeric immunoglobulin receptor, and collagen alpha-1(VI) chain in plasma samples from pancreaticcancer patients and healthy controls showed a significant increase.
References
More filters
Journal ArticleDOI
UCSF Chimera--a visualization system for exploratory research and analysis.
Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Journal ArticleDOI
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
Mapping and quantifying mammalian transcriptomes by RNA-Seq.
TL;DR: Although >90% of uniquely mapped reads fell within known exons, the remaining data suggest new and revised gene models, including changed or additional promoters, exons and 3′ untranscribed regions, as well as new candidate microRNA precursors.
Journal ArticleDOI
Cancer statistics, 2008.
Ahmedin Jemal,Rebecca L. Siegel,Elizabeth Ward,Yongping Hao,Jiaquan Xu,Taylor Murray,Michael J. Thun +6 more
TL;DR: This report examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends.
Related Papers (5)
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
D. Williams Parsons,Siân Jones,Xiaosong Zhang,Jimmy Lin,Rebecca J. Leary,Philipp Angenendt,Parminder Mankoo,Hannah Carter,I-Mei Siu,Gary L. Gallia,Alessandro Olivi,Roger E. McLendon,B.K. Ahmed Rasheed,Stephen T. Keir,Tatiana Nikolskaya,Yuri Nikolsky,Dana A. Busam,Hanna Tekleab,Luis A. Diaz,James Hartigan,Doug R. Smith,Robert L. Strausberg,Suely Kazue Nagahashi Marie,Sueli Mieko Oba Shinjo,Hai Yan,Gregory J. Riggins,Darell D. Bigner,Rachel Karchin,Nick Papadopoulos,Giovanni Parmigiani,Bert Vogelstein,Victor E. Velculescu,Kenneth W. Kinzler +32 more
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Thierry Conroy,Françoise Desseigne,Marc Ychou,Olivier Bouché,Rosine Guimbaud,Yves Becouarn,Antoine Adenis,Jean-Luc Raoul,Sophie Gourgou-Bourgade,Jaafar Bennouna,Jean-Baptiste Bachet,Faiza Khemissa-Akouz,Denis Péré-Vergé,Catherine Delbaldo,Eric Assenat,Bruno Chauffert,C. Montoto-Grillot,Michel Ducreux +17 more