Institution
Cancer Research UK
Nonprofit•London, United Kingdom•
About: Cancer Research UK is a nonprofit organization based out in London, United Kingdom. It is known for research contribution in the topics: Cancer & Gene. The organization has 1025 authors who have published 777 publications receiving 148154 citations. The organization is also known as: CRUK.
Topics: Cancer, Gene, Breast cancer, DNA repair, Nucleotide excision repair
Papers published on a yearly basis
Papers
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TL;DR: It is shown that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1, a potent human immunodeficiency virus–1 (HIV-1)–suppressive chemokine and ligand for the HIV coreceptor CCR5.
Abstract: Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1αP), a potent human immunodeficiency virus–1 (HIV-1)–suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.
1,205 citations
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TL;DR: The protein coding exome is sequenced in a series of primary ccRCC and the identification of the SWI/SNF chromatin remodelling complex gene PBRM1 is reported as a second majorccRCC cancer gene, with truncating mutations in 41% (92/227) of cases.
Abstract: The genetics of renal cancer is dominated by inactivation of the VHL tumour suppressor gene in clear cell carcinoma (ccRCC), the commonest histological subtype. A recent large-scale screen of ∼3,500 genes by PCR-based exon re-sequencing identified several new cancer genes in ccRCC including UTX (also known as KDM6A), JARID1C (also known as KDM5C) and SETD2 (ref. 2). These genes encode enzymes that demethylate (UTX, JARID1C) or methylate (SETD2) key lysine residues of histone H3. Modification of the methylation state of these lysine residues of histone H3 regulates chromatin structure and is implicated in transcriptional control. However, together these mutations are present in fewer than 15% of ccRCC, suggesting the existence of additional, currently unidentified cancer genes. Here, we have sequenced the protein coding exome in a series of primary ccRCC and report the identification of the SWI/SNF chromatin remodelling complex gene PBRM1 (ref. 4) as a second major ccRCC cancer gene, with truncating mutations in 41% (92/227) of cases. These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology.
1,186 citations
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The Royal Marsden NHS Foundation Trust1, University of Texas MD Anderson Cancer Center2, Duke University3, Stanford University4, Cancer Research UK5, University of Pennsylvania6, Harvard University7, Peter MacCallum Cancer Centre8, University of Chicago9, Memorial Sloan Kettering Cancer Center10, Queen Mary University of London11, University College London12, Indiana University13, University Health Network14, Imperial College London15, University of Melbourne16
TL;DR: Nine major recommendations that should be taken to improve the outcome for women with ovarian cancer are outlined in this Opinion article.
Abstract: There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article.
1,130 citations
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TL;DR: A phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck found substantial objective responses, including a high proportion of complete responses.
Abstract: ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to selectively replicate in and lyse p53-deficient cancer cells while sparing normal cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity in patients with recurrent head and neck cancer, disease recurs rapidly with either therapy alone. We undertook a phase II trial of a combination of intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients with recurrent squamous cell cancer of the head and neck. There were substantial objective responses, including a high proportion of complete responses. By 6 months, none of the responding tumors had progressed, whereas all non-injected tumors treated with chemotherapy alone had progressed. The toxic effects that occurred were acceptable. Tumor biopsies obtained after treatment showed tumor-selective viral replication and necrosis induction.
1,110 citations
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TL;DR: It was found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence, and the proportion of C>T transitions at CpG sites increased during tumor progression.
Abstract: Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73-75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development.
1,105 citations
Authors
Showing all 1051 results
Name | H-index | Papers | Citations |
---|---|---|---|
Douglas G. Altman | 253 | 1001 | 680344 |
Nicholas J. Wareham | 212 | 1657 | 204896 |
Richard Peto | 183 | 683 | 231434 |
Kay-Tee Khaw | 174 | 1389 | 138782 |
Gregory J. Hannon | 165 | 421 | 140456 |
Douglas F. Easton | 165 | 844 | 113809 |
Timothy J. Key | 146 | 808 | 90810 |
Alan Ashworth | 134 | 578 | 72089 |
Brigid L.M. Hogan | 132 | 333 | 66486 |
Paul D.P. Pharoah | 130 | 794 | 71338 |
David P. Lane | 129 | 568 | 90787 |
Jack Cuzick | 128 | 754 | 79979 |
Carlos Caldas | 122 | 547 | 73840 |
Gillian Murphy | 122 | 373 | 47043 |
Walter F. Bodmer | 121 | 579 | 68679 |