ALBERT

Description: Despite its unprecedented growth in output per capita in the last two decades, China has essentially followed the life satisfaction trajectory of the central and eastern European transition countries—a U-shaped swing and a nil or declining trend. There is no evidence of an increase in life satisfaction of the magnitude that might have been expected to result from the fourfold improvement in the level of per capita consumption that has occurred. As in the European countries, in China the trend and U-shaped pattern appear to be related to a pronounced rise in unemployment followed by a mild decline, and an accompanying dissolution of the social safety net along with growing income inequality. The burden of worsening life satisfaction in China has fallen chiefly on the lowest socioeconomic groups. An initially highly egalitarian distribution of life satisfaction has been replaced by an increasingly unequal one, with decreasing life satisfaction in persons in the bottom third of the income distribution and increasing life satisfaction in those in the top third.

Description: In light of the recent discovery of ArH + in the Crab nebula, it is shown through high-level quantum chemical comptuations that the global minima on the Ar + /Ne +  + H 2 potential energy surfaces are ArH 2 + and NeH 2 + . Hence, ArH 2 + may be a necessary intermediate in the Ar +  + H 2 -〉 ArH +  + H formation reaction proposed in the same work where ArH + is first reported in the Crab nebula. ArH 2 + is also probably an intermediate in the alternative $\mathrm{Ar} + \mathrm{H}_2^+ \rightarrow \mathrm{ArH}^+ + \mathrm{H}$ reaction. Additionally, it is shown that Ne $^+ + \mathrm{H}_2 \rightarrow \mathrm{NeH}_2^+$ will subsequently most likely yield $\mathrm{Ne} + \mathrm{H}_2^+$ and not NeH +  + H offering a possible rationale as to the absence of NeH + in spectra obtained from the interstellar medium (ISM). Following from this, spectroscopic data (both rotational and vibrational) are provided for NeH 2 + and ArH 2 + through the use of highly accurate quantum chemical quartic and cubic force fields. All possible isotopologues are also included for 20 Ne, 22 Ne, 36 Ar, 38 Ar, 40 Ar, 1 H, and D. The dipole moments for these systems are quite large at 5.61 D for NeH 2 + and 4.37 D for ArH 2 + . The spectroscopic constants provided will aid in the potential detection of these open-shell noble gas dihydride cations in the ISM.

Description: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biankin, Andrew V -- Waddell, Nicola -- Kassahn, Karin S -- Gingras, Marie-Claude -- Muthuswamy, Lakshmi B -- Johns, Amber L -- Miller, David K -- Wilson, Peter J -- Patch, Ann-Marie -- Wu, Jianmin -- Chang, David K -- Cowley, Mark J -- Gardiner, Brooke B -- Song, Sarah -- Harliwong, Ivon -- Idrisoglu, Senel -- Nourse, Craig -- Nourbakhsh, Ehsan -- Manning, Suzanne -- Wani, Shivangi -- Gongora, Milena -- Pajic, Marina -- Scarlett, Christopher J -- Gill, Anthony J -- Pinho, Andreia V -- Rooman, Ilse -- Anderson, Matthew -- Holmes, Oliver -- Leonard, Conrad -- Taylor, Darrin -- Wood, Scott -- Xu, Qinying -- Nones, Katia -- Fink, J Lynn -- Christ, Angelika -- Bruxner, Tim -- Cloonan, Nicole -- Kolle, Gabriel -- Newell, Felicity -- Pinese, Mark -- Mead, R Scott -- Humphris, Jeremy L -- Kaplan, Warren -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chou, Angela -- Chin, Venessa T -- Chantrill, Lorraine A -- Mawson, Amanda -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Daly, Roger J -- Merrett, Neil D -- Toon, Christopher -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Australian Pancreatic Cancer Genome Initiative -- Kakkar, Nipun -- Zhao, Fengmei -- Wu, Yuan Qing -- Wang, Min -- Muzny, Donna M -- Fisher, William E -- Brunicardi, F Charles -- Hodges, Sally E -- Reid, Jeffrey G -- Drummond, Jennifer -- Chang, Kyle -- Han, Yi -- Lewis, Lora R -- Dinh, Huyen -- Buhay, Christian J -- Beck, Timothy -- Timms, Lee -- Sam, Michelle -- Begley, Kimberly -- Brown, Andrew -- Pai, Deepa -- Panchal, Ami -- Buchner, Nicholas -- De Borja, Richard -- Denroche, Robert E -- Yung, Christina K -- Serra, Stefano -- Onetto, Nicole -- Mukhopadhyay, Debabrata -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Gallinger, Steven -- Hruban, Ralph H -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Schulick, Richard D -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Capelli, Paola -- Corbo, Vincenzo -- Scardoni, Maria -- Tortora, Giampaolo -- Tempero, Margaret A -- Mann, Karen M -- Jenkins, Nancy A -- Perez-Mancera, Pedro A -- Adams, David J -- Largaespada, David A -- Wessels, Lodewyk F A -- Rust, Alistair G -- Stein, Lincoln D -- Tuveson, David A -- Copeland, Neal G -- Musgrove, Elizabeth A -- Scarpa, Aldo -- Eshleman, James R -- Hudson, Thomas J -- Sutherland, Robert L -- Wheeler, David A -- Pearson, John V -- McPherson, John D -- Gibbs, Richard A -- Grimmond, Sean M -- 13031/Cancer Research UK/United Kingdom -- 2P50CA101955/CA/NCI NIH HHS/ -- P01CA134292/CA/NCI NIH HHS/ -- P50 CA101955/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50CA062924/CA/NCI NIH HHS/ -- R01 CA097075/CA/NCI NIH HHS/ -- R01 CA97075/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):399-405. doi: 10.1038/nature11547. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103869" target="_blank"〉PubMed〈/a〉

Description: In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA- SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blaese, R M -- Culver, K W -- Miller, A D -- Carter, C S -- Fleisher, T -- Clerici, M -- Shearer, G -- Chang, L -- Chiang, Y -- Tolstoshev, P -- Greenblatt, J J -- Rosenberg, S A -- Klein, H -- Berger, M -- Mullen, C A -- Ramsey, W J -- Muul, L -- Morgan, R A -- Anderson, W F -- New York, N.Y. -- Science. 1995 Oct 20;270(5235):475-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Center for Human Genome Research, National Institutes of Health (NIH), Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7570001" target="_blank"〉PubMed〈/a〉

Description: Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523082/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523082/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waddell, Nicola -- Pajic, Marina -- Patch, Ann-Marie -- Chang, David K -- Kassahn, Karin S -- Bailey, Peter -- Johns, Amber L -- Miller, David -- Nones, Katia -- Quek, Kelly -- Quinn, Michael C J -- Robertson, Alan J -- Fadlullah, Muhammad Z H -- Bruxner, Tim J C -- Christ, Angelika N -- Harliwong, Ivon -- Idrisoglu, Senel -- Manning, Suzanne -- Nourse, Craig -- Nourbakhsh, Ehsan -- Wani, Shivangi -- Wilson, Peter J -- Markham, Emma -- Cloonan, Nicole -- Anderson, Matthew J -- Fink, J Lynn -- Holmes, Oliver -- Kazakoff, Stephen H -- Leonard, Conrad -- Newell, Felicity -- Poudel, Barsha -- Song, Sarah -- Taylor, Darrin -- Waddell, Nick -- Wood, Scott -- Xu, Qinying -- Wu, Jianmin -- Pinese, Mark -- Cowley, Mark J -- Lee, Hong C -- Jones, Marc D -- Nagrial, Adnan M -- Humphris, Jeremy -- Chantrill, Lorraine A -- Chin, Venessa -- Steinmann, Angela M -- Mawson, Amanda -- Humphrey, Emily S -- Colvin, Emily K -- Chou, Angela -- Scarlett, Christopher J -- Pinho, Andreia V -- Giry-Laterriere, Marc -- Rooman, Ilse -- Samra, Jaswinder S -- Kench, James G -- Pettitt, Jessica A -- Merrett, Neil D -- Toon, Christopher -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Jamieson, Nigel B -- Graham, Janet S -- Niclou, Simone P -- Bjerkvig, Rolf -- Grutzmann, Robert -- Aust, Daniela -- Hruban, Ralph H -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Corbo, Vincenzo -- Bassi, Claudio -- Falconi, Massimo -- Zamboni, Giuseppe -- Tortora, Giampaolo -- Tempero, Margaret A -- Australian Pancreatic Cancer Genome Initiative -- Gill, Anthony J -- Eshleman, James R -- Pilarsky, Christian -- Scarpa, Aldo -- Musgrove, Elizabeth A -- Pearson, John V -- Biankin, Andrew V -- Grimmond, Sean M -- 103721/Wellcome Trust/United Kingdom -- C29717/A17263/Cancer Research UK/United Kingdom -- C596/A18076/Cancer Research UK/United Kingdom -- P30 CA006973/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- P50 CA062924/CA/NCI NIH HHS/ -- P50 CA62924/CA/NCI NIH HHS/ -- England -- Nature. 2015 Feb 26;518(7540):495-501. doi: 10.1038/nature14169.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia [2] QIMR Berghofer Medical Research Institute, Herston Road, Brisbane 4006, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2010, Australia. ; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia [3] South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia [4] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; 1] Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia [2] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] Department of Anatomical Pathology, St Vincent's Hospital, Sydney, New South Wales 2010, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. ; 1] Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia [2] University of Sydney, Sydney, New South Wales 2006, Australia. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] University of Sydney, Sydney, New South Wales 2006, Australia [3] Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia. ; 1] Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia [2] School of Medicine, University of Western Sydney, Penrith, New South Wales 2175, Australia. ; Department of Surgery, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia. ; Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. ; Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. ; 1] School of Surgery M507, University of Western Australia, 35 Stirling Highway, Nedlands 6009, Australia [2] St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia [3] Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital, Subiaco, Western Australia 6008, Australia. ; 1] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK [2] Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK [3] West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. ; 1] Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK [2] Department of Medical Oncology, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. ; Norlux Neuro-Oncology Laboratory, CRP-Sante Luxembourg, 84 Val Fleuri, L-1526, Luxembourg. ; Norlux Neuro-Oncology, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5019 Bergen, Norway. ; Departments of Surgery and Pathology, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. ; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; Departments of Pathology and Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston Texas 77030, USA. ; The David M. Rubenstein Pancreatic Cancer Research Center and Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; 1] ARC-NET Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy [2] Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy. ; ARC-NET Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Surgery and Oncology, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. ; 1] Department of Surgery and Oncology, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy [2] Departments of Surgery and Pathology, Ospedale Sacro Cuore Don Calabria Negrar, Verona 37024, Italy. ; 1] Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy [2] Departments of Surgery and Pathology, Ospedale Sacro Cuore Don Calabria Negrar, Verona 37024, Italy. ; Department of Oncology, University and Hospital Trust of Verona, Verona 37134, Italy. ; Division of Hematology and Oncology, University of California, San Francisco, California 94122, USA. ; 1] The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, University of New South Wales, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia [2] University of Sydney, Sydney, New South Wales 2006, Australia. ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25719666" target="_blank"〉PubMed〈/a〉

Description: Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267026/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morgan, Richard A -- Dudley, Mark E -- Wunderlich, John R -- Hughes, Marybeth S -- Yang, James C -- Sherry, Richard M -- Royal, Richard E -- Topalian, Suzanne L -- Kammula, Udai S -- Restifo, Nicholas P -- Zheng, Zhili -- Nahvi, Azam -- de Vries, Christiaan R -- Rogers-Freezer, Linda J -- Mavroukakis, Sharon A -- Rosenberg, Steven A -- Z01 BC010763-01/Intramural NIH HHS/ -- Z01 SC003811-32/Intramural NIH HHS/ -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2006 Oct 6;314(5796):126-9. Epub 2006 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16946036" target="_blank"〉PubMed〈/a〉

Description: Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bailey, Peter -- Chang, David K -- Nones, Katia -- Johns, Amber L -- Patch, Ann-Marie -- Gingras, Marie-Claude -- Miller, David K -- Christ, Angelika N -- Bruxner, Tim J C -- Quinn, Michael C -- Nourse, Craig -- Murtaugh, L Charles -- Harliwong, Ivon -- Idrisoglu, Senel -- Manning, Suzanne -- Nourbakhsh, Ehsan -- Wani, Shivangi -- Fink, Lynn -- Holmes, Oliver -- Chin, Venessa -- Anderson, Matthew J -- Kazakoff, Stephen -- Leonard, Conrad -- Newell, Felicity -- Waddell, Nick -- Wood, Scott -- Xu, Qinying -- Wilson, Peter J -- Cloonan, Nicole -- Kassahn, Karin S -- Taylor, Darrin -- Quek, Kelly -- Robertson, Alan -- Pantano, Lorena -- Mincarelli, Laura -- Sanchez, Luis N -- Evers, Lisa -- Wu, Jianmin -- Pinese, Mark -- Cowley, Mark J -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chantrill, Lorraine A -- Mawson, Amanda -- Humphris, Jeremy -- Chou, Angela -- Pajic, Marina -- Scarlett, Christopher J -- Pinho, Andreia V -- Giry-Laterriere, Marc -- Rooman, Ilse -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Merrett, Neil D -- Toon, Christopher W -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Moran-Jones, Kim -- Jamieson, Nigel B -- Graham, Janet S -- Duthie, Fraser -- Oien, Karin -- Hair, Jane -- Grutzmann, Robert -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Corbo, Vincenzo -- Bassi, Claudio -- Rusev, Borislav -- Capelli, Paola -- Salvia, Roberto -- Tortora, Giampaolo -- Mukhopadhyay, Debabrata -- Petersen, Gloria M -- Australian Pancreatic Cancer Genome Initiative -- Munzy, Donna M -- Fisher, William E -- Karim, Saadia A -- Eshleman, James R -- Hruban, Ralph H -- Pilarsky, Christian -- Morton, Jennifer P -- Sansom, Owen J -- Scarpa, Aldo -- Musgrove, Elizabeth A -- Bailey, Ulla-Maja Hagbo -- Hofmann, Oliver -- Sutherland, Robert L -- Wheeler, David A -- Gill, Anthony J -- Gibbs, Richard A -- Pearson, John V -- Waddell, Nicola -- Biankin, Andrew V -- Grimmond, Sean M -- 103721/Z/14/Z/Wellcome Trust/United Kingdom -- A12481/Cancer Research UK/United Kingdom -- A18076/Cancer Research UK/United Kingdom -- C29717/A17263/Cancer Research UK/United Kingdom -- England -- Nature. 2016 Mar 3;531(7592):47-52. doi: 10.1038/nature16965. Epub 2016 Feb 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia. ; Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK. ; The Kinghorn Cancer Centre, 370 Victoria St, Darlinghurst, and the Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. ; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, New South Wales 2200, Australia. ; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, New South Wales 2170, Australia. ; QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia. ; Department of Molecular and Human Genetics, Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Michael DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. ; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA. ; Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA. ; Genetic and Molecular Pathology, SA Pathology, Adelaide, South Australia 5000, Australia. ; School of Biological Sciences, The University of Adelaide, Adelaide, South Australia 5000, Australia. ; Harvard Chan Bioinformatics Core, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA. ; Macarthur Cancer Therapy Centre, Campbelltown Hospital, New South Wales 2560, Australia. ; Department of Pathology. SydPath, St Vincent's Hospital, Sydney, NSW 2010, Australia. ; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2052, Australia. ; School of Environmental &Life Sciences, University of Newcastle, Ourimbah, New South Wales 2258, Australia. ; Department of Surgery, Royal North Shore Hospital, St Leonards, Sydney, New South Wales 2065, Australia. ; University of Sydney, Sydney, New South Wales 2006, Australia. ; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown New South Wales 2050, Australia. ; School of Medicine, University of Western Sydney, Penrith, New South Wales 2175, Australia. ; Fiona Stanley Hospital, Robin Warren Drive, Murdoch, Western Australia 6150, Australia. ; Department of Gastroenterology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia. ; Department of Surgery, Princess Alexandra Hospital, Ipswich Rd, Woollongabba, Queensland 4102, Australia. ; School of Surgery M507, University of Western Australia, 35 Stirling Hwy, Nedlands 6009, Australia and St John of God Pathology, 12 Salvado Rd, Subiaco, Western Australia 6008, Australia. ; Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow G4 OSF, UK. ; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK. ; Department of Medical Oncology, Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow G12 0YN, UK. ; Department of Pathology, Southern General Hospital, Greater Glasgow &Clyde NHS, Glasgow G51 4TF, UK. ; GGC Bio-repository, Pathology Department, Southern General Hospital, 1345 Govan Road, Glasgow G51 4TY, UK. ; Department of Surgery, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. ; Departments of Pathology and Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston Texas 77030, USA. ; The David M. Rubenstein Pancreatic Cancer Research Center and Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. ; ARC-Net Applied Research on Cancer Centre, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Pathology and Diagnostics, University of Verona, Verona 37134, Italy. ; Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona 37134, Italy. ; Department of Medical Oncology, Comprehensive Cancer Centre, University and Hospital Trust of Verona, Verona 37134, Italy. ; Mayo Clinic, Rochester, Minnesota 55905, USA. ; Elkins Pancreas Center, Baylor College of Medicine, One Baylor Plaza, MS226, Houston, Texas 77030-3411, USA. ; Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK. ; Institute for Cancer Science, University of Glasgow, Glasgow G12 8QQ, UK. ; University of Melbourne, Parkville, Victoria 3010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26909576" target="_blank"〉PubMed〈/a〉