CHROMOTHRIPSIS

Dissecting the Molecular Mechanism of Catastrophic DNA Rearrangement in Cancer

 Coordinatore EUROPEAN MOLECULAR BIOLOGY LABORATORY 

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 Nazionalità Coordinatore Germany [DE]
 Totale costo 1˙496˙880 €
 EC contributo 1˙496˙880 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-StG
 Funding Scheme ERC-SG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-04-01   -   2019-03-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    EUROPEAN MOLECULAR BIOLOGY LABORATORY

 Organization address address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117

contact info
Titolo: Dr.
Nome: Jan Oliver
Cognome: Korbel
Email: send email
Telefono: +49 6221 387 8822
Fax: +49 6221 387 8575

DE (HEIDELBERG) hostInstitution 1˙496˙880.00
2    EUROPEAN MOLECULAR BIOLOGY LABORATORY

 Organization address address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117

contact info
Titolo: Ms.
Nome: Virginia
Cognome: Otón García
Email: send email
Telefono: +49 6221 387 8535
Fax: +49 6221 387 8575

DE (HEIDELBERG) hostInstitution 1˙496˙880.00

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

massive    signalling    occurring    mechanistic    cancers    chromothripsis    involving    genome    alterations    cell    pathways    contexts    data    linked   

 Obiettivo del progetto (Objective)

'Recent cancer genome analyses have led to the discovery of a process involving massive genome structural rearrangement (SR) formation in a one-step, cataclysmic event, coined chromothripsis. The term chromothripsis (chromo from chromosome; thripsis for shattering into pieces) stands for a hypothetical process in which individual chromosomes are pulverised, resulting in a multitude of fragments, some of which are lost to the cell whereas others are erroneously rejoined. Compelling evidence was presented that chromothripsis plays a crucial role in the development, or progression of a notable subset of human cancers – thus, tumorigensis models involving gradual acquisitions of alterations may need to be revised in these cancers.

Presently, chromothripsis lacks a mechanistic basis. We recently showed that in childhood medulloblastoma brain tumours driven by Sonic Hedgehog (Shh) signalling, chromothripsis is linked with predisposing TP53 mutations. Thus, rather than occurring in isolation, chromothripsis appears to be prone to happen in conjunction with (or instigated by) gradually acquired alterations, or in the context of active signalling pathways, the inference of which may lead to further mechanistic insights. Using such rationale, I propose to dissect the mechanism behind chromothripsis using interdisciplinary approaches. First, we will develop a computational approach to accurately detect chromothripsis. Second, we will use this approach to link chromothripsis with novel factors and contexts. Third, we will develop highly controllable cell line-based systems to test concrete mechanistic hypotheses, thereby taking into account our data on linked factors and contexts. Fourth, we will generate transcriptome data to monitor pathways involved in inducing chromothripsis, and such involved in coping with the massive SRs occurring. We will also combine findings from all these approaches to build a comprehensive model of chromothripsis and its associated pathways.'

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