The discovery of mutations in cancer genes has advanced our understanding of cancer. These results are dispersed across the scientific literature and with the availability of the human genome ...sequence will continue to accrue. The COSMIC (Catalogue of Somatic Mutations in Cancer) database and website have been developed to store somatic mutation data in a single location and display the data and other information related to human cancer. To populate this resource, data has currently been extracted from reports in the scientific literature for somatic mutations in four genes, BRAF, HRAS, KRAS2 and NRAS. At present, the database holds information on 66 634 samples and reports a total of 10 647 mutations. Through the web pages, these data can be queried, displayed as figures or tables and exported in a number of formats. COSMIC is an ongoing project that will continue to curate somatic mutation data and release it through the website.
COSMIC 2005 FORBES, S; CLEMENTS, J; STRATTON, M. R ...
British journal of cancer,
01/2006, Letnik:
94, Številka:
2
Journal Article
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The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. Over the past 25 years, approximately 350 ...cancer genes have been identified, of which 311 are somatically mutated. COSMIC has been expanded and now holds data previously reported in the scientific literature for 28 known cancer genes. In addition, there is data from the systematic sequencing of 518 protein kinase genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency above 5% in one or more tumour type, no mutations were found in 333 genes and 180 are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site has been expanded to give more views and summaries of the data and provide faster query routes and downloads. In addition, there is a new section describing mutations found through a screen of known cancer genes in 728 cancer cell lines including the NCI-60 set of cancer cell lines.
Cancer and genomics Stratton, Michael R; Futreal, P. Andrew; Kasprzyk, Arek ...
Nature (London),
02/2001, Letnik:
409, Številka:
6822
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Identification of the genes that cause oncogenesis is a central aim of cancer research. We searched the proteins predicted from the draft human genome sequence for paralogues of known tumour ...suppressor genes, but no novel genes were identified. We then assessed whether it was possible to search directly for oncogenic sequence changes in cancer cells by comparing cancer genome sequences against the draft genome. Apparently chimaeric transcripts (from oncogenic fusion genes generated by chromosomal translocations, the ends of which mapped to different genomic locations) were detected to the same degree in both normal and neoplastic tissues, indicating a significant level of false positives. Our experiment underscores the limited amount and variable quality of DNA sequence from cancer cells that is currently available.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of ...the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.
The penetrance of the BRCA2 gene on chromosome 13q12-13 has been estimated in two large, systematically ascertained, linked families, by use of a maximum-likelihood method to incorporate both ...cancer-incidence data and 13q marker typings in the families. The cumulative risk of breast cancer in female gene carriers was estimated to be 59.8% by age 50 years (95% confidence interval 95% CI 25.9%-78.5%) and 79.5% by age 70 years (95% CI 28.9%-97.5%). The cumulative risk of breast cancer in male carriers was estimated to be 6.3% (95% CI 1.4%-25.6%) by age 70 years. There was no evidence of any risk difference between the two families. These results indicate that the lifetime breast cancer risk in BRCA2 carriers, for at least a subset of mutations, is comparable to that for BRCA1. A significant excess of ovarian cancer in gene carriers was observed (relative risk 17.69, based on three cases), but the absolute risk of ovarian cancer was less than that reported for BRCA1. Significant excesses of laryngeal cancer (relative risk 7.67, based on two possible carriers) and prostate cancer (relative risk 2.89, based on five possible carriers) were also observed. One case of ocular melanoma, as well as a second eye cancer of unspecified histology, occurred in obligate gene carriers.
The allele sizes of polymorphic microsatellite repeats in DNA from human cancers were compared to normal DNA from the same patients. In 16 out of 196 paired samples (8%), we found evidence of an ...extra allele of a different size in the tumour which was not present in the normal DNA. Sequence analysis confirmed that the extra allele originates from the appropriate locus and that the size change is attributable to alteration in the number of repeat units. This form of instability was more common in tri- and tetranucleotide repeats than in dinucleotide repeats. In any single tumour sample only one repeat in the set examined was abnormal, the remainder showing identical patterns in normal and tumour DNA or evidence of allele loss. The pattern of instability in diverse types of cancer differs from that reported in colorectal neoplasms.
Following on from the 50th anniversary of the birth of Theatre in Education in Britain in 2015, this is an essential and timely companion to the story of TIE. It contextualizes it within the ...political and educational landscape of the last fifty years and examines its legacy today. Through this, Roger Wooster offers insights into future possibilities and applications in the field of Applied Theatre, drama in schools and pedagogical theory. With examples and analysis of international developments in TIE, and a foreword by Philip Taylor (NYU, USA), the volume provides a wide-ranging account of past and current practice. Across its three sections the volume examines the origins, work and legacy of TIE, considering for the first time its practical details. Each section features an Afterword by a leading practitioner reflecting on the work (including Warwick Dobson, Chris Vine and Anthony Jackson), and chapters draw on case studies and interviews with key practitioners. Chapter summaries and a companion website further enhance the text as a valuable teaching resource for theatre educators.
A census of human cancer genes Stratton, Michael R; Futreal, P. Andrew; Coin, Lachlan ...
Nature reviews. Cancer,
03/2004, Letnik:
4, Številka:
3
Journal Article
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A central aim of cancer research has been to identify the mutated genes that are causally implicated in oncogenesis ('cancer genes'). After two decades of searching, how many have been identified and ...how do they compare to the complete gene set that has been revealed by the human genome sequence? We have conducted a 'census' of cancer genes that indicates that mutations in more than 1% of genes contribute to human cancer. The census illustrates striking features in the types of sequence alteration, cancer classes in which oncogenic mutations have been identified and protein domains that are encoded by cancer genes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Breast and Ovarian Cancer Wooster, Richard; Weber, Barbara L
The New England journal of medicine,
06/2003, Letnik:
348, Številka:
23
Journal Article
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Breast and ovarian cancers are among the most common cancers in women. It is known that a woman is at higher risk for breast or ovarian cancer if a family member has had the disease. This article in ...the Genomic Medicine series provides up-to-date information on the heritable factors associated with these tumors.
Despite years of intensive study and substantial progress in understanding susceptibility to breast and ovarian cancer, these diseases remain important causes of death in women. However, several recent critical advances — sequencing of the human genome and the development of high-throughput techniques for identifying DNA-sequence variants, changes in copy numbers, and global expression profiles — have dramatically accelerated the pace of research aimed at preventing and curing these diseases. We review some of the important discoveries in the genetics of breast and ovarian cancer, ongoing studies to isolate additional susceptibility genes, and early work on molecular profiling involving microarrays.
Susceptibility . . .
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