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COSMIC Release v82

3 Aug 2017

What's new in v82? As ever, our curation team has been hard at work producing full literature curation of four new genes, a significant update to a fifth and a new fusion pair, as well as incorporating 342 genomes from 11 systematic screen papers. The updates from the ICGC release 24 have also been included.

The new genes include: BTK, a TEC family cytoplasmic tyrosine kinase required for the development, activation and differentiation of B cells. Recurrent mutations at BTK C481 have been identified in patients with chronic lymphocytic leukaemia who have progressed after an initial response to ibrutinib treatment.  DROSHA, together with its co-factor DGCR8, is involved in the early stages of miRNA processing and is essential for the biogenesis of most miRNAs. It is frequently mutated in Wilms tumour, with the majority of mutations found in the RNase IIIb domain, at p.E1147. EPAS1, encodes Hypoxia-inducible factor 2-alpha, and somatic mutations in EPAS1 occur recurrently in sporadic pheochromocytomas and paragangliomas, as well as in somatostatinomas as part of Pacak-Zhuang syndrome (multiple paragangliomas and somatostatinomas associated with polycythaemia). Finally KEAP1, a component of the Cullin 3-based E3 ubiquitin ligase complex which controls the stability and accumulation of NRF2 protein, important in redox balancing. Somatic mutations of the KEAP1 gene are found in non-small cell lung cancer, hepatocellular carcinoma, endometrial cancer, melanoma and many other cancer types and have been associated with a poor outcome and resistance to chemotherapy. 

There has also been a substantial update for SMAD4. An important tumour suppressor gene, and one of the major driver genes in pancreatic cancer. A lack of SMAD4 mutations in high-grade pancreatic intraepithelial neoplasia, the major precursor of pancreatic ductal adenocarcinoma, indicates these are late genetic alterations in pancreatic carcinoma. 

We have also included the fusion pair NUP214-ABL1. This fusion results from a recurrent genetic abnormality at 9q34 and is found predominantly in T-cell acute lymphoblastic leukaemia (T-ALL), with a reported frequency of up to 10%. In T-ALL, the NUP214-ABL1 fusion is associated with elevated expression of HOXA cluster genes and with corticosteroid/chemotherapy resistance. SET encodes a protein with a critical role in chromatin binding and remodelling, while NUP214 encodes an FG-repeat-containing nucleoporin involved in the cell cycle and transportation of material between the nucleus and cytoplasm.

With the completion of the new COSMIC website we have now switched it over as the main site with the old COSMIC site becoming legacy. The changes have been designed to give the website a modern look and feel, and to allow for the incorporation of new tools that are under development for COSMIC. For further details about the new site and maintenance of the old site please see our article here

The drug resistance pages now include a new gene-drug pair: BTK - Ibrutinib and updates have been added for Gefitinib, Osimertinib, Endocrine therapy and Crizotinib. We are still looking at changing how we display the drug resistance information in order to make it more useful and intuitive, if you have any thoughts on this, please let us know.

Finally, as part of the development of the Hallmarks of Cancer feature the Cancer Gene Census has had a re-evalutaion, based on strict criteria evaluating the strength of evidence supporting each genes role as a driver in cancer. This has resulted in the introduction of a tier system based on the supporting evidence.  A full discussion of the implications and rationale behind the decision to make the changes is available here, along with details of genes that have moved tiers. 

For technical details please see the release notes.

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COSMIC, the Catalogue Of Somatic Mutations In Cancer, is the most comprehensive resource for exploring the impact of somatic mutations in human cancer. Here on our news page we aim to give you an insight into what we are doing and why. We will keep you updated with new developments and release information as well as any events we are hosting.