Publikationsserver der Universitätsbibliothek Marburg
Titel:Vergleich numerischer und struktureller Aberrationen in HPV-positiven und HPV-negativen Kopf-Hals-Tumorzelllinien
Autor:Patze, Johannes
Weitere Beteiligte: Wittig, Andrea (Prof. Dr.)
Veröffentlicht:2018
URI:https://archiv.ub.uni-marburg.de/diss/z2018/0259
URN: urn:nbn:de:hebis:04-z2018-02592
DOI: https://doi.org/10.17192/z2018.0259
DDC: Medizin
Titel (trans.):Comparison of numerical und structural aberrations in HPV-positive und HPV-negative head and neck cancer cell lines
Publikationsdatum:2018-12-10
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
humane Papillomaviren, chromosomale Instabilität, Kopf-Hals Tumore, m-FISH, chromosomale instability, HNSCC, HPV, HNSCC, chromosomale Instabilität, HPV, Kopf-Hals Tumore, genomische Stabilität, genomische Stabilität, m-FISH, HPV, humane Papillomaviren, HNSCC

Zusammenfassung:
Kopf-Hals-Tumore (HNSCC) können durch die klassischen Noxen Tabak und Alkohol aber auch durch eine Infektion mit dem humanen Papillomavirus induziert werden. Die zweite Gruppe stellt eine eigene Tumorentität dar mit bevorzugter Lokalisation im Oropharynx. Während HNSCC-Tumore weltweit rückläufig sind, steigt die Zahl HPV-assoziierter Tumore in Europa, Japan und den USA deutlich an. Diese Patienten sind in der Regel jünger und haben weniger Begleiterkrankungen, vor allem aber zeigen sie nach Radiochemotherapie eine deutlich bessere Prognose. Daten des The Cancer Genome Atlas (TCGA) zeigen, dass diese beiden Tumorentitäten sich offensichtlich nicht bezüglich Mutationslast oder Veränderung der Kopienzahl von Chromosomen unterscheiden, wohl aber in der Genexpression. Ziel der vorliegenden Arbeit war es, erstmalig anhand von jeweils fünf Zelllinien zu überprüfen, inwieweit sich HPV-negative und -positive Zellen bezüglich DNA-Gehalt sowie numerischer und struktureller Chromosomenaberrationen unterscheiden. Der DNA-Gehalt wurde mittels Flusszytometrie und die numerischen und strukturellen Aberrationen mittels G-Banden-gefärbten Metaphase-Präparaten bzw. m-FISH geprüft. Für beide Entitäten wird sowohl im DNA-Gehalt als auch in der Zahl der Chromosomen eine große Variation gefunden, wobei diese beiden Parameter eng miteinander korrelieren. Im Mittel besteht allerdings sowohl bezüglich DNA-Gehalt als auch Zahl der Chromosomen kein signifikanter Unterschied zwischen HPV-negativen und –positiven HNSCC-Zelllinien. Die Aneuploidie, wie sie mittels m-FISH für jedes Chromosom bestimmt wurde, zeigte je nach Chromosom eine große Variation zwischen diploidem, triploidem und tetraploidem Status. Besonders erstaunlich ist, dass bis auf Chromosom 7 diese Variation für HPV-negative und HPV-positive Zelllinien nahezu identisch ist. Diese Variation stimmte zudem mit den beiden einzigen bisher veröffentlichen Datensätzen überein. Daher wird für diese Variation bei HNSCC-Zellen von einer Gesetzmäßigkeit auszugegangen, die zudem unabhängig vom HPV-Status ist. Der Nachweis der strukturellen Chromosomenaberration zeigte für HPV-negative Zelllinien insgesamt ein sehr heterogenes Bild, während für HPV-positive Linien eine besondere Präferenz für die Chromosomen 2, 3 und 5 beobachtet wird. Insbesondere für Chromosom 3 wurden für HPV-positive Zellen signifikant mehr Translokationen nachgewiesen als für HPV-negative Linien. Es wird vermutet, dass in der chromosomalen Instabilität dieser Region die Ursache für die höhere Radiochemieempfindlichkeit HPV-positiver Tumore begründet ist.

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