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Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
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. Expand
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse.
It is found that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer. Expand
Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice.
Targeted concomitant endogenous expression of Trp53(R172H) and Kras(G12D) to the mouse pancreas reveals the cooperative development of invasive and widely metastatic carcinoma that recapitulates the human disease. Expand
Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer
Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, it is found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. Expand
DAXX/ATRX, MEN1, and mTOR Pathway Genes Are Frequently Altered in Pancreatic Neuroendocrine Tumors
Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis and a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors was found. Expand
Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
To explore the genetic origins of head and neck squamous cell carcinoma, whole-exome sequencing and gene copy number analyses were used to study 32 primary tumors and identified mutations in FBXW7 and NotCH1, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type. Expand
Genomic analyses identify molecular subtypes of pancreatic cancer
Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S… Expand
A draft map of the human proteome
A draft map of the human proteome is presented using high-resolution Fourier-transform mass spectrometry to discover a number of novel protein-coding regions, which includes translated pseudogenes, non-c coding RNAs and upstream open reading frames. Expand
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
Oncogene-directed increased expression of Nrf2 is a new mechanism for the activation of the NRF2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-RasG12D and B-RafV619E, and in human pancreatic cancer. Expand
DPC4, A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1
DPC4 is identified as a candidate tumor suppressor gene whose inactivation may play a role in pancreatic and possibly other human cancers. Expand