Journal ArticleDOI
p53 polymorphisms: cancer implications
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TLDR
Polymorphic variants of other genes in the p53 pathway, such as MDM2, which might have biological consequences either individually or in combination with p53 variants are discussed.Abstract:
The normal functioning of p53 is a potent barrier to cancer. Tumour-associated mutations in TP53, typically single nucleotide substitutions in the coding sequence, are a hallmark of most human cancers and cause dramatic defects in p53 function. By contrast, only a small fraction, if any, of the >200 naturally occurring sequence variations (single nucleotide polymorphisms, SNPs) of TP53 in human populations are expected to cause measurable perturbation of p53 function. Polymorphisms in the TP53 locus that might have cancer-related phenotypical manifestations are the subject of this Review. Polymorphic variants of other genes in the p53 pathway, such as MDM2, which might have biological consequences either individually or in combination with p53 variants are also discussed.read more
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Journal ArticleDOI
The first 30 years of p53: growing ever more complex
Arnold J. Levine,Moshe Oren +1 more
TL;DR: Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus, and new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation.
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TP53 Mutations in Human Cancers: Origins, Consequences, and Clinical Use
TL;DR: Current knowledge on TP53 gene variations observed in human cancers and populations, and current clinical applications derived from this knowledge are summarized.
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Genetic variation in microRNA networks: the implications for cancer research
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When mutants gain new powers: news from the mutant p53 field
Ran Brosh,Varda Rotter +1 more
TL;DR: Recent studies on mutant p53 regulation, gain-of-function mechanisms, transcriptional effects and prognostic association are reviewed, with a focus on the clinical implications of these findings.
Journal ArticleDOI
Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence
TL;DR: The findings underscore the crucial role of acetylation in differentially modulating p53 responses and suggest that unconventional activities of p53, such as metabolic regulation and antioxidant function, are critical for suppression of early-onset spontaneous tumorigenesis.
References
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Journal ArticleDOI
Surfing the p53 network
TL;DR: The p53 tumour-suppressor gene integrates numerous signals that control cell life and death, and the disruption of p53 has severe consequences when a highly connected node in the Internet breaks down.
Journal ArticleDOI
The International HapMap Project
John W. Belmont,Paul Hardenbol,Thomas D. Willis,Fuli Yu,Huanming Yang,Lan Yang Ch'Ang,Wei Huang,Bin Liu,Yan Shen,Paul K.H. Tam,Lap-Chee Tsui,Mary M.Y. Waye,Jeffrey Tze Fei Wong,Changqing Zeng,Qingrun Zhang,Mark S. Chee,Luana Galver,Semyon Kruglyak,Sarah S. Murray,Arnold Oliphant,Alexandre Montpetit,Fanny Chagnon,Vincent Ferretti,Martin Leboeuf,Michael S. Phillips,Andrei Verner,Shenghui Duan,Denise L. Lind,Raymond D. Miller,John P. Rice,Nancy L. Saccone,Patricia Taillon-Miller,Ming Xiao,Akihiro Sekine,Koki Sorimachi,Yoichi Tanaka,Tatsuhiko Tsunoda,Eiji Yoshino,David R. Bentley,Sarah E. Hunt,Don Powell,Houcan Zhang,Ichiro Matsuda,Yoshimitsu Fukushima,Darryl Macer,Eiko Suda,Charles N. Rotimi,Clement Adebamowo,Toyin Aniagwu,Patricia A. Marshall,Olayemi Matthew,Chibuzor Nkwodimmah,Charmaine D.M. Royal,Mark Leppert,Missy Dixon,Fiona Cunningham,Ardavan Kanani,Gudmundur A. Thorisson,Peter E. Chen,David J. Cutler,Carl S. Kashuk,Peter Donnelly,Jonathan Marchini,Gilean McVean,Simon Myers,Lon R. Cardon,Andrew P. Morris,Bruce S. Weir,James C. Mullikin,Michael Feolo,Mark J. Daly,Renzong Qiu,Alastair Kent,Georgia M. Dunston,Kazuto Kato,Norio Niikawa,Jessica Watkin,Richard A. Gibbs,Erica Sodergren,George M. Weinstock,Richard K. Wilson,Lucinda Fulton,Jane Rogers,Bruce W. Birren,Hua Han,Hongguang Wang,Martin Godbout,John C. Wallenburg,Paul L'Archevêque,Guy Bellemare,Kazuo Todani,Takashi Fujita,Satoshi Tanaka,Arthur L. Holden,Francis S. Collins,Lisa D. Brooks,Jean E. McEwen,Mark S. Guyer,Elke Jordan,Jane Peterson,Jack Spiegel,Lawrence M. Sung,Lynn F. Zacharia,Karen Kennedy,Michael Dunn,Richard Seabrook,Mark Shillito,Barbara Skene,John Stewart,David Valle,Ellen Wright Clayton,Lynn B. Jorde,Aravinda Chakravarti,Mildred K. Cho,Troy Duster,Troy Duster,Morris W. Foster,Maria Jasperse,Bartha Maria Knoppers,Pui-Yan Kwok,Julio Licinio,Jeffrey C. Long,Pilar N. Ossorio,Vivian Ota Wang,Charles N. Rotimi,Patricia Spallone,Patricia Spallone,Sharon F. Terry,Eric S. Lander,Eric H. Lai,Deborah A. Nickerson,Gonçalo R. Abecasis,David Altshuler,Michael Boehnke,Panos Deloukas,Julie A. Douglas,Stacey Gabriel,Richard R. Hudson,Thomas J. Hudson,Leonid Kruglyak,Yusuke Nakamura,Robert L. Nussbaum,Stephen F. Schaffner,Stephen T. Sherry,Lincoln Stein,Toshihiro Tanaka +145 more
TL;DR: The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Journal ArticleDOI
A second generation human haplotype map of over 3.1 million SNPs
Kelly A. Frazer,Dennis G. Ballinger,David R. Cox,David A. Hinds,Laura L. Stuve,Richard A. Gibbs,John W. Belmont,Andrew Boudreau,Paul Hardenbol,Suzanne M. Leal,Shiran Pasternak,David A. Wheeler,Thomas D. Willis,Fuli Yu,Huanming Yang,Changqing Zeng,Gao Yang,H. B. Hu,Weitao Hu,Chaohua Li,Wei Lin,Siqi Liu,Hao Pan,Xiaoli Tang,Jian Wang,Wei Wang,Jun Yu,Bo Zhang,Qingrun Zhang,Hongbin Zhao,Hui Zhao,Jun Zhou,Stacey Gabriel,Rachel Barry,Brendan Blumenstiel,Amy L. Camargo,Matthew Defelice,Maura Faggart,Mary Goyette,Supriya Gupta,Jamie Moore,Huy Nguyen,Robert C. Onofrio,Melissa Parkin,Jessica Roy,Erich Stahl,Ellen Winchester,Liuda Ziaugra,David Altshuler,Yan Shen,Zhijian Yao,Wei Huang,Xun Chu,Yungang He,Li Jin,Yangfan Liu,Yayun Shen,Weiwei Sun,Haifeng Wang,Yi Wang,Ying Wang,Xiaoyan Xiong,Liang Xu,Mary M.Y. Waye,Stephen Kwok-Wing Tsui,Hong Xue,J. Tze Fei Wong,Luana Galver,Jian-Bing Fan,Kevin L. Gunderson,Sarah S. Murray,Arnold Oliphant,Mark S. Chee,Alexandre Montpetit,Fanny Chagnon,Vincent Ferretti,Martin Leboeuf,Jean François Olivier,Michael S. Phillips,Stéphanie Roumy,Clémentine Sallée,Andrei Verner,Thomas J. Hudson,Pui-Yan Kwok,Dongmei Cai,Daniel C. Koboldt,Raymond D. Miller,Ludmila Pawlikowska,Patricia Taillon-Miller,Ming Xiao,Lap-Chee Tsui,William Mak,Qiang Song You,Paul K.H. Tam,Yusuke Nakamura,Takahisa Kawaguchi,Takuya Kitamoto,Takashi Morizono,Atsushi Nagashima,Yozo Ohnishi,Akihiro Sekine,Toshihiro Tanaka,Tatsuhiko Tsunoda,Panos Deloukas,Christine P. Bird,Marcos Delgado,Emmanouil T. Dermitzakis,Rhian Gwilliam,Sarah E. Hunt,Jonathan J. Morrison,Don Powell,Barbara E. Stranger,Pamela Whittaker,David R. Bentley,Mark J. Daly,Paul I.W. de Bakker,Jeffrey C. Barrett,Yves Chretien,Julian Maller,Steve McCarroll,Nick Patterson,Itsik Pe'er,Alkes L. Price,Shaun Purcell,Daniel J. Richter,Pardis C. Sabeti,Richa Saxena,Stephen F. Schaffner,Pak C. Sham,Patrick Varilly,Lincoln Stein,Lalitha Krishnan,Albert V. Smith,Marcela K. Tello-Ruiz,Gudmundur A. Thorisson,Aravinda Chakravarti,Peter E. Chen,David J. Cutler,Carl S. Kashuk,Shin Lin,Gonçalo R. Abecasis,Weihua Guan,Yun Li,Heather M. Munro,Zhaohui S. Qin,Daryl J. Thomas,Gilean McVean,Adam Auton,Leonardo Bottolo,Niall Cardin,Susana Eyheramendy,Colin Freeman,Jonathan Marchini,Simon Myers,Chris C. A. Spencer,Matthew Stephens,Peter Donnelly,Lon R. Cardon,Geraldine M. Clarke,David M. Evans,Andrew P. Morris,Bruce S. Weir,Todd A. Johnson,James C. Mullikin,Stephen T. Sherry,Michael Feolo,Andrew D. Skol,Houcan Zhang,Ichiro Matsuda,Yoshimitsu Fukushima,Darryl Macer,Eiko Suda,Charles N. Rotimi,Clement Adebamowo,Ike Ajayi,Toyin Aniagwu,Patricia A. Marshall,Chibuzor Nkwodimmah,Charmaine D.M. Royal,Mark Leppert,Missy Dixon,Andy Peiffer,Renzong Qiu,Alastair Kent,Kazuto Kato,Norio Niikawa,Isaac F. Adewole,Bartha Maria Knoppers,Morris W. Foster,Ellen Wright Clayton,Jessica Watkin,Donna M. Muzny,Lynne V. Nazareth,Erica Sodergren,George M. Weinstock,Imtaz Yakub,Bruce W. Birren,Richard K. Wilson,Lucinda Fulton,Jane Rogers,John Burton,Nigel P. Carter,C M Clee,Mark Griffiths,Matthew C. Jones,Kirsten McLay,Robert W. Plumb,Mark T. Ross,Sarah Sims,David Willey,Zhu Chen,Hua Han,Le Kang,Martin Godbout,John C. Wallenburg,Paul L'Archevêque,Guy Bellemare,Koji Saeki,Hongguang Wang,Daochang An,Hongbo Fu,Qing Li,Zhen Wang,Renwu Wang,Arthur L. Holden,Lisa D. Brooks,Jean E. McEwen,Mark S. Guyer,Vivian Ota Wang,Jane Peterson,Michael Shi,Jack Spiegel,Lawrence M. Sung,Lynn F. Zacharia,Francis S. Collins,Karen Kennedy,Ruth Jamieson,John Stewart +237 more
TL;DR: The Phase II HapMap is described, which characterizes over 3.1 million human single nucleotide polymorphisms genotyped in 270 individuals from four geographically diverse populations and includes 25–35% of common SNP variation in the populations surveyed, and increased differentiation at non-synonymous, compared to synonymous, SNPs is demonstrated.
Journal ArticleDOI
Cancer genes and the pathways they control.
TL;DR: The purposes of this review are to highlight examples of progress in many areas of cancer research, indicate where knowledge is scarce and point out fertile grounds for future investigation.
Journal ArticleDOI
A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity
Chava Kimchi-Sarfaty,Jung Mi Oh,In-Wha Kim,Zuben E. Sauna,Anna Maria Calcagno,Suresh V. Ambudkar,Michael M. Gottesman +6 more
TL;DR: It is hypothesized that the presence of a rare codon, marked by the synonymous polymorphism, affects the timing of cotranslational folding and insertion of P-gp into the membrane, thereby altering the structure of substrate and inhibitor interaction sites.