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
More filters
••
TL;DR: This study identifies SMCHD1 as an epigenetic modifier of the D4Z4 metastable epiallele and as a causal genetic determinant of FSHD2 and possibly other human diseases subject to epigenetic regulation.
Abstract: Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle The more common form, autosomal dominant FSHD1, is caused by contraction of the D4Z4 array, whereas the genetic determinants and inheritance of D4Z4 array contraction-independent FSHD2 are unclear Here, we show that mutations in SMCHD1 (encoding structural maintenance of chromosomes flexible hinge domain containing 1) on chromosome 18 reduce SMCHD1 protein levels and segregate with genome-wide D4Z4 CpG hypomethylation in human kindreds FSHD2 occurs in individuals who inherited both the SMCHD1 mutation and a normal-sized D4Z4 array on a chromosome 4 haplotype permissive for DUX4 expression Reducing SMCHD1 levels in skeletal muscle results in D4Z4 contraction-independent DUX4 expression Our study identifies SMCHD1 as an epigenetic modifier of the D4Z4 metastable epiallele and as a causal genetic determinant of FSHD2 and possibly other human diseases subject to epigenetic regulation
519 citations
••
University of Washington1, Johns Hopkins University2, University of Texas Health Science Center at Houston3, University of British Columbia4, Washington University in St. Louis5, National Institutes of Health6, University of Michigan7, Vanderbilt University8, University of Southern California9, University of Hawaii at Manoa10, Mayo Clinic11, Northwestern University12, University of Pittsburgh13, University of Iowa14, Statens Serum Institut15, Harvard University16, Fred Hutchinson Cancer Research Center17, Memorial Sloan Kettering Cancer Center18, Broad Institute19
TL;DR: Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) is detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies to identify common deleted regions with genes previously associated with hematological cancers.
Abstract: We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).
519 citations
••
TL;DR: How muscle necrosis can negatively impact the kidney, potentially culminating in tubular necrosis and ARF is discussed, to review current and possible future pharmacologic approaches for the management of this dramatic and often life threatening "myo-renal syndrome".
519 citations
••
TL;DR: Three studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans, and five patients showed durable engraftment until the time of death 82 to 386 days posttransplant.
519 citations
••
University of California, Los Angeles1, Fred Hutchinson Cancer Research Center2, University of Cincinnati3, Stony Brook University4, University of Pittsburgh5, Harvard University6, Stanford University7, University of Massachusetts Medical School8, University of Wisconsin-Madison9, University of Tennessee Health Science Center10, University at Buffalo11, University of Texas Health Science Center at San Antonio12, Wayne State University13, Baylor College of Medicine14, Yeshiva University15, University of California, Davis16
TL;DR: Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive, and breast cancer mortality also appears to be increased with combined use of estrogen plus proggestin.
Abstract: Context In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported. Objective To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009. Design, Setting, and Participants A total of 16 608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12 788 (83%) of the surviving participants. Main Outcome Measures Invasive breast cancer incidence and breast cancer mortality. Results In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group. Conclusions Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin. Trial Registration clinicaltrials.gov Identifier: NCT00000611
518 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 |