Institution
Fred Hutchinson Cancer Research Center
Nonprofit•Cape Town, South Africa•
About: Fred Hutchinson Cancer Research Center is a nonprofit organization based out in Cape Town, South Africa. It is known for research contribution in the topics: Population & Transplantation. The organization has 12322 authors who have published 30954 publications receiving 2288772 citations. The organization is also known as: Fred Hutch & The Hutch.
Topics: Population, Transplantation, Cancer, Breast cancer, Prostate cancer
Papers published on a yearly basis
Papers
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Memorial Sloan Kettering Cancer Center1, Swiss Institute of Bioinformatics2, Harvard University3, Princeton University4, University of Texas at Dallas5, Washington University in St. Louis6, Institute for Systems Biology7, Bilkent University8, Van Andel Institute9, University of Pennsylvania10, University of Texas MD Anderson Cancer Center11, Mayo Clinic12, Columbia University Medical Center13, Fred Hutchinson Cancer Research Center14, University of California, San Francisco15, University of Michigan16, Peter MacCallum Cancer Centre17, Baylor College of Medicine18
TL;DR: This work charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity.
1,841 citations
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TL;DR: This article conducted a meta-analysis of coronary artery disease (CAD) cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 millions low-frequency (0.005 < MAF < 0.5) variants.
Abstract: Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
1,839 citations
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TL;DR: A rather restrictive criterion is proposed for use of the adjective 'surrogate' - it is proposed that a surrogate for a true endpoint yield a valid test of the null hypothesis of no association between treatment and the true response.
Abstract: I discuss the idea of using surrogate endpoints in the context of clinical trials to compare two or more treatments or interventions in respect to some 'true' endpoint, typically a disease occurrence. In order that treatment comparison based on a surrogate response variable have a meaningful implication for the corresponding true endpoint treatment comparison, a rather restrictive criterion is proposed for use of the adjective 'surrogate'. Specifically, I propose that a surrogate for a true endpoint yield a valid test of the null hypothesis of no association between treatment and the true response. This criterion essentially requires the surrogate variable to 'capture' any relationship between the treatment and the true endpoint, a notion that can be operationalized by requiring the true endpoint rate at any follow-up time to be independent of treatment, given the preceding history of the surrogate variable. I then discuss this operational criterion in the examples of the accompanying papers and in the setting of trials aimed at the primary and secondary prevention of cancer.
1,816 citations
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TL;DR: This work suggests that non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.
Abstract: Cancer is widely perceived as a heterogeneous group of disorders with markedly different biological properties, which are caused by a series of clonally selected genetic changes in key tumour-suppressor genes and oncogenes. However, recent data suggest that cancer has a fundamentally common basis that is grounded in a polyclonal epigenetic disruption of stem/progenitor cells, mediated by 'tumour-progenitor genes'. Furthermore, tumour cell heterogeneity is due in part to epigenetic variation in progenitor cells, and epigenetic plasticity together with genetic lesions drives tumour progression. This crucial early role for epigenetic alterations in cancer is in addition to epigenetic alterations that can substitute for genetic variation later in tumour progression. Therefore, non-neoplastic but epigenetically disrupted stem/progenitor cells might be a crucial target for cancer risk assessment and chemoprevention.
1,806 citations
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Pardis C. Sabeti1, Pardis C. Sabeti2, Patrick Varilly2, Patrick Varilly1 +255 more•Institutions (50)
TL;DR: ‘Long-range haplotype’ methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population are developed.
Abstract: With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.
1,778 citations
Authors
Showing all 12368 results
Name | H-index | Papers | Citations |
---|---|---|---|
Walter C. Willett | 334 | 2399 | 413322 |
Robert Langer | 281 | 2324 | 326306 |
Meir J. Stampfer | 277 | 1414 | 283776 |
JoAnn E. Manson | 270 | 1819 | 258509 |
David J. Hunter | 213 | 1836 | 207050 |
Peer Bork | 206 | 697 | 245427 |
Eric Boerwinkle | 183 | 1321 | 170971 |
Ruedi Aebersold | 182 | 879 | 141881 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Aaron R. Folsom | 181 | 1118 | 134044 |
David Baker | 173 | 1226 | 109377 |
Frederick W. Alt | 171 | 577 | 95573 |
Lily Yeh Jan | 162 | 467 | 73655 |
Yuh Nung Jan | 162 | 460 | 74818 |
Charles N. Serhan | 158 | 728 | 84810 |