University of Cambridge > Talks.cam > Seminars on Quantitative Biology @ CRUK Cambridge Institute  > Analysis of a large cancer gene screen in myelodysplastic syndromes

  Browse A-Z

Log in

Cambridge users (raven)details Other usersdetails No account?details

Information on

Subscribing to talksdetails Finding a talkdetails Adding a talkdetails Disseminating talksdetails Help and Documentationdetails

Analysis of a large cancer gene screen in myelodysplastic syndromes

Add to your list(s) Download to your calendar using vCal

If you have a question about this talk, please contact Florian Markowetz.

Myelodysplastic syndromes (MDS) are a heterogeneous group of blood cancers leading to an ineffective production of blood cells. I will present computational methods and results from a large screen of 111 cancer genes sequenced at 250x coverage in 738 MDS patients. To analyse such data we have developed a new variant caller which analyses all samples jointly to estimate the local distributions of sequencing artefacts, for an increased specificity. At the same time this method gains power from incorporating prior knowledge about mutational hotspots. The resulting mutational landscape of MDS displays complex patterns of pairwise association between genes, indicative of epistatic interactions involving components of the spliceosome machinery and epigenetic modifiers. Coupled with inferences on subclonal mutations, these data suggest a hypothesis of genetic ‘predestination’, in which early driver mutations, typically affecting genes involved in RNA splicing, dictate future trajectories of disease evolution with distinct clinical phenotypes. Driver mutations had equivalent prognostic significance whether clonal or subclonal, and leukemia-free survival deteriorated steadily as numbers of driver mutations increased. Thus, analysis of oncogenic mutations in large, well-characterized cohorts of patients illustrates the interconnections between the cancer genome and disease biology, with considerable potential for clinical application.

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

Tell a friend about this talk:

This talk is included in these lists:

Note that ex-directory lists are not shown.

Other lists

Chemistry Speech Seminars Type the title of a new list here Cambridge PhD Training Programme in Chemical Biology & Molecular Medicine Europe Research Seminar Series

Other talks

Singularities of Hermitian-Yang-Mills connections and the Harder-Narasimhan-Seshadri filtration Breast cancer - demographics, presentation, diagnosis and patient pathway Modulating developmental signals allows establishment of cultures of expanded potential stem cells Girton College 57th Founders’ Memorial Lecture with Hisham Matar: Life and Work Interconversion of Light and Electricity in Molecular Semiconductors The formation of high density dust rings and clumps: the role of vorticity Speculations about homological mirror symmetry for affine hypersurfaces The Productivity Paradox: are we too busy to get anything done? Refugees and Migration Active bacterial suspensions: from individual effort to team work Glucagon like peptide-1 receptor - a possible role for beta cell physiology in susceptibility to autoimmune diabetes Brain tumours: demographics, presentation, diagnosis, treatment
 

© 2006-2024 Talks.cam, University of Cambridge. Contact Us | Help and Documentation | Privacy and Publicity