| |  Online-Ressource |
|---|
| Verfasst von: | Bolkestein, Michiel [VerfasserIn]  |
|---|
| | Wong, John [VerfasserIn] |
|---|
| | Thewes, Verena [VerfasserIn] |
|---|
| | Körber, Verena [VerfasserIn] |
|---|
| | Hlevnjak, Mario [VerfasserIn] |
|---|
| | Elgaafary, Shaymaa [VerfasserIn] |
|---|
| | Schulze, Markus [VerfasserIn] |
|---|
| | Kommoss, Felix [VerfasserIn] |
|---|
| | Sinn, Peter [VerfasserIn] |
|---|
| | Anzeneder, Tobias [VerfasserIn] |
|---|
| | Hirsch, Steffen [VerfasserIn] |
|---|
| | Devens, Frauke [VerfasserIn] |
|---|
| | Schröter, Petra [VerfasserIn] |
|---|
| | Höfer, Thomas [VerfasserIn] |
|---|
| | Schneeweiss, Andreas [VerfasserIn] |
|---|
| | Lichter, Peter [VerfasserIn] |
|---|
| | Zapatka, Marc [VerfasserIn] |
|---|
| | Ernst, Aurélie [VerfasserIn] |
|---|
| Titel: | Chromothripsis in human breast cancer |
|---|
| Verf.angabe: | Michiel Bolkestein, John K.L. Wong, Verena Thewes, Verena Körber, Mario Hlevnjak, Shaymaa Elgaafary, Markus Schulze, Felix K.F. Kommoss, Hans-Peter Sinn, Tobias Anzeneder, Steffen Hirsch, Frauke Devens, Petra Schröter, Thomas Höfer, Andreas Schneeweiss, Peter Lichter, Marc Zapatka, and Aurélie Ernst |
|---|
| E-Jahr: | 2020 |
|---|
| Jahr: | September 24, 2020 |
|---|
| Umfang: | 14 S. |
|---|
| Fussnoten: | Gesehen am 04.02.2021 |
|---|
| Titel Quelle: | Enthalten in: Cancer research |
|---|
| Ort Quelle: | Philadelphia, Pa. : AACR, 1916 |
|---|
| Jahr Quelle: | 2020 |
|---|
| Band/Heft Quelle: | 80(2020), 22, Seite 4918-4931 |
|---|
| ISSN Quelle: | 1538-7445 |
|---|
| Abstract: | Chromothripsis is a form of genome instability by which a presumably single catastrophic event generates extensive genomic rearrangements of one or a few chromosomes. Widely assumed to be an early event in tumor development, this phenomenon plays a prominent role in tumor onset. In this study, an analysis of chromothripsis in 252 human breast cancers from two patient cohorts (149 metastatic breast cancers, 63 untreated primary tumors, 29 local relapses, and 11 longitudinal pairs) using whole-genome and whole-exome sequencing reveals that chromothripsis affects a substantial proportion of human breast cancers, with a prevalence over 60% in a cohort of metastatic cases and 25% in a cohort comprising predominantly luminal breast cancers. In the vast majority of cases, multiple chromosomes per tumor were affected, with most chromothriptic events on chromosomes 11 and 17 including, among other significantly altered drivers, CCND1, ERBB2, CDK12, and BRCA1. Importantly, chromothripsis generated recurrent fusions that drove tumor development. Chromothripsis-related rearrangements were linked with univocal mutational signatures, with clusters of point mutations due to kataegis in close proximity to the genomic breakpoints and with the activation of specific signaling pathways. Analyzing the temporal order of events in tumors with and without chromothripsis as well as longitudinal analysis of chromothriptic patterns in tumor pairs offered important insights into the role of chromothriptic chromosomes in tumor evolution. - Significance: These findings identify chromothripsis as a major driving event in human breast cancer. |
|---|
| DOI: | doi:10.1158/0008-5472.CAN-20-1920 |
|---|
| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1158/0008-5472.CAN-20-1920 |
|---|
| | Volltext: https://cancerres.aacrjournals.org/content/80/22/4918 |
|---|
| | DOI: https://doi.org/10.1158/0008-5472.CAN-20-1920 |
|---|
| Datenträger: | Online-Ressource |
|---|
| Sprache: | eng |
|---|
| K10plus-PPN: | 1747406821 |
|---|
| Verknüpfungen: | → Zeitschrift |
|---|
Chromothripsis in human breast cancer / Bolkestein, Michiel [VerfasserIn]; September 24, 2020 (Online-Ressource)
