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
Clinical and molecular characterization of HER2 amplified-pancreatic cancer.
Angela Chou,Angela Chou,Angela Chou,Nicola Waddell,Mark J. Cowley,Mark J. Cowley,Anthony J. Gill,Anthony J. Gill,Anthony J. Gill,David K. Chang,David K. Chang,David K. Chang,Ann-Marie Patch,Katia Nones,Jianmin Wu,Jianmin Wu,Mark Pinese,Mark Pinese,Amber L. Johns,David Miller,Karin S. Kassahn,Adnan Nagrial,Adnan Nagrial,Harpreet Wasan,David Goldstein,Christopher W. Toon,Christopher W. Toon,Venessa T. Chin,Venessa T. Chin,Lorraine A. Chantrill,Lorraine A. Chantrill,Jeremy L. Humphris,R. Scott Mead,R. Scott Mead,R. Scott Mead,Ilse Rooman,Ilse Rooman,Jaswinder S. Samra,Marina Pajic,Marina Pajic,Elizabeth A. Musgrove,Elizabeth A. Musgrove,John V. Pearson,Adrienne Morey,Sean M. Grimmond,Sean M. Grimmond,Andrew V. Biankin,Andrew V. Biankin,Andrew V. Biankin +48 more
TL;DR: Recruiting patients based on HER2 amplification, rather than organ of origin, could make trials of anti-HER2 therapies feasible in less common cancer types, and have implications for clinical practice.
Journal ArticleDOI
Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer cell growth and proliferation
Cindy Benod,Maia V. Vinogradova,Natalia Jouravel,Grace E. Kim,Robert J. Fletterick,Elena P. Sablin +5 more
TL;DR: It is shown that LRH-1 transcription is activated up to 30-fold in human pancreatic cancer cells compared to normal pancreatic ductal epithelium, suggesting the LRH the1 receptor as a plausible therapeutic target for treatment of pancreaticductal adenocarcinomas in vivo.
Journal ArticleDOI
The sodium leak channel, NALCN, in health and disease.
Maud Cochet-Bissuel,Maud Cochet-Bissuel,Philippe Lory,Philippe Lory,Arnaudarnaud Monteil,Arnaudarnaud Monteil +5 more
TL;DR: Although the physiological role of the NALCN channelosome is poorly understood, its involvement in human diseases should foster interest for drug development in the near future.
Journal ArticleDOI
Advancing a clinically relevant perspective of the clonal nature of cancer.
Christian Ruiz,Christian Ruiz,Elizabeth Lenkiewicz,Lisa Evers,Tara Holley,Alex Robeson,Jeff Kiefer,Michael J. Demeure,Michael A. Hollingsworth,Michael Shen,Donna Prunkard,Peter S. Rabinovitch,Tobias Zellweger,Spyro Mousses,Jeffrey M. Trent,Jeffrey M. Trent,John D. Carpten,Lukas Bubendorf,Daniel D. Von Hoff,Michael T. Barrett +19 more
TL;DR: It is proposed that high-definition analyses of the genomes of distinct clonal populations of cancer cells in patients in vivo can help guide diagnoses and tailor approaches to personalized treatment.
Journal ArticleDOI
Sleeping giants: emerging roles for the fat cadherins in health and disease.
TL;DR: Recent progress on understanding the role of the Fat cadherin family is summarized, integrating the current knowledge of molecular interactions and tissue distributions, together with the accumulating evidence of their changed expression in human disease.
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