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
Crosstalk of Sp1 and Stat3 signaling in pancreatic cancer pathogenesis.
Chen Huang,Keping Xie +1 more
TL;DR: Targeting both Sp1 and Stat3, central transcription factors that regulate a number of pathways important to tumorigenesis, are a potential preventive and therapeutic strategy for pancreatic cancer.
Journal ArticleDOI
Proliferation and tissue remodeling in cancer: the hallmarks revisited.
TL;DR: It is demonstrated that proliferation and remodeling signatures are partially independent and result in four distinctive cancer subtypes, notably, the proliferation signature correlates with poor outcome in lung, prostate, breast and brain cancer, whereas remodeling increases mortality rates in colorectal and ovarian cancer.
Journal ArticleDOI
Second generation sequencing of the mesothelioma tumor genome.
Raphael Bueno,Assunta De Rienzo,Lingsheng Dong,Gavin J. Gordon,Colin F. Hercus,William G. Richards,Roderick V. Jensen,Arif Anwar,Gautam Maulik,Lucian R. Chirieac,Kim-Fong Ho,Bruce E. Taillon,Cynthia L. Turcotte,Robert Hercus,Steven R. Gullans,David J. Sugarbaker +15 more
TL;DR: Second-generation sequencing uncovered all types of mutations in this human primary malignant pleural mesothelioma tumor, with DNA rearrangements representing the dominant type.
Journal ArticleDOI
Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma
Jean-Baptiste Bachet,Raphaël Maréchal,Pieter Demetter,F. Bonnetain,Anne Couvelard,Magali Svrcek,Armelle Bardier-Dupas,Pascal Hammel,Alain Sauvanet,C. Louvet,François Paye,Philippe Rougier,Christophe Penna,Jean-Christophe Vaillant,Thierry André,Jean Closset,Isabelle Salmon,Jean-François Emile,J.-L. Van Laethem +18 more
TL;DR: CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma.
Journal ArticleDOI
Menin determines K-RAS proliferative outputs in endocrine cells
Chester E. Chamberlain,David W. Scheel,Kathleen McGlynn,Hail Kim,Takeshi Miyatsuka,Juehu Wang,Vinh Son Nguyen,Shuhong Zhao,Anastasia Mavropoulos,Aswin George Abraham,Eric O'Neill,Gregory M. Ku,Melanie H. Cobb,Gail R. Martin,Michael S. German +14 more
TL;DR: It is found that K-RAS paradoxically suppressed, rather than promoted, growth in pancreatic endocrine cells, and potential strategies both for regenerating pancreatic β cells for people with diabetes and for targeting menin-sensitive endocrine tumors are suggested.
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