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Junior Research Group Genome Instability in Tumors

PD Dr. Aurélie Ernst

Unknown before the next-generation sequencing era, chromothripsis is a new phenomenon of genome instability, by which a presumably single catastrophic event generates extensive genomic rearrangements of one or a few chromosome(s).

Chromothripsis is frequent in cancer and linked with poor prognosis in a number of tumour types. The research in our group aims at achieving a better understanding of how chromothripsis arises and at assessing potential implications for cancer patients.

More specifically, our goals are 1) to characterize in which context chromothripsis occurs and which evolutionary dynamics chromothriptic tumors may have 2) to decipher the mechanistic basis of chromothripsis 3) to target vulnerabilities of tumor cells with chromothripsis.

For this, we employ approaches encompassing single-cell genomics, functional testing in model systems and pre-clinical studies in mice.

Contact

PD Dr. Aurélie Ernst

Genome Instability in Tumors (B420)

Deutsches Krebsforschungszentrum

Im Neuenheimer Feld 580

69120 Heidelberg

Tel: +49 6221 42 1512

E-Mail: a.ernst (at) dkfz.de

Selected Publications

Rausch T, Snajder R, Leger A, Simovic M, Giurgiu M, Villacorta L, Henssen AG, Fröhling S, Stegle O, Birney E, Bonder MJ*, Ernst A*, Korbel JO*. Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures. Cell Genomics. 2023 March 22 doi:https://doi.org/10.1016/j.xgen.2023.100281 *joined last and corresponding authors
Simovic M, Bolkestein M, Moustafa M, Wong JKL, Körber V, Benedetto S, Khalid U, Schreiber HS, Jugold M, Korshunov A, Hübschmann D, Mack N, Brons S, Wei PC, Breckwoldt MO, Heiland S, Bendszus M, Jürgen D, Höfer T, Zapatka M, Kool M, Pfister SM, Abdollahi A, Ernst A. Carbon ion radiotherapy eradicates medulloblastomas with chromothripsis in an orthotopic Li-Fraumeni patient-derived mouse model. Neuro Oncol. 2021 May 28:noab127. doi: 10.1093/neuonc/noab127. PMID: 34049392
Bolkestein M, Wong JKL, Thewes V, Körber V, Hlevnjak M, Elgaafary S, Schulze M, Kommoss FKF, Sinn HP, Anzeneder T, Hirsch S, Devens F, Schröter P, Höfer T, Schneeweiss A, Lichter P, Zapatka M, Ernst A. Chromothripsis in Human Breast Cancer. Cancer Res. 2020 Nov 15;80(22):4918-4931. doi: 10.1158/0008-5472.CAN-20-1920. PMID: 32973084
Voronina N, Wong JKL, Hübschmann D, Hlevnjak M, Uhrig S, Heilig CE, Horak P, Kreutzfeldt S, Mock A, Stenzinger A, Hutter B, Fröhlich M, Brors B, Jahn A, Klink B, Gieldon L, Sieverling L, Feuerbach L, Chudasama P, Beck K, Kroiss M, Heining C, Möhrmann L, Fischer A, Schröck E, Glimm H, Zapatka M, Lichter P, Fröhling S, Ernst A. The landscape of chromothripsis across adult cancer types. Nat Commun. 2020 May 8;11(1):2320. doi: 10.1038/s41467-020-16134-7.