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Deletion lengthening at chromosomes 6q and 16q targets multiple tumor suppressor genes and is associated with an increasingly poor prognosis in prostate cancer

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Martina Kluth
  • Simon Jung
  • Omar Habib
  • Mina Eshagzaiy
  • Anna Heinl
  • Nina Amschler
  • Sawinee Masser
  • Malte Mader
  • Frederic Runte
  • Philipp Barow
  • Sohall Frogh
  • Jazan Omari
  • Christina Möller-Koop
  • Claudia Hube-Magg
  • Jan Korbel
  • Stefan Steurer
  • Till Krech
  • Hartwig Huland
  • Markus Graefen
  • Sarah Minner
  • Guido Sauter
  • Thorsten Schlomm
  • Ronald Simon

Prostate cancer is characterized by recurrent deletions that can considerably vary in size. We hypothesized that large deletions develop from small deletions and that this "deletion lengthening" might have a "per se" carcinogenic role through a combinatorial effect of multiple down regulated genes.In vitroknockdown of 37 genes located inside the 6q12-q22 deletion region identified 4 genes with additive tumor suppressive effects, further supporting a role of the deletion size for cancer aggressiveness. Employing fluorescencein-situhybridization analysis on prostate cancer tissue microarrays, we determined the deletion size at 6q and 16q in more than 3,000 tumors. 16q and 6q deletion length was strongly linked to poor clinical outcome and this effect was even stronger if the length of both deletions was combined. To study deletion lengthening in cancer progression we eventually analyzed the entire cancers from 317 patients for 6q and 16q deletion length heterogeneity and found that the deletion expanded within 50-60% of 6q and 16q deleted cancers. Taken together, these data suggest continuous "deletion lengthening" as a key mechanism for prostate cancer progression leading to parallel down regulation of genes with tumor suppressive properties, some of which act cooperatively.

OriginalsprogEngelsk
TidsskriftOncoTarget
Vol/bind8
Udgave nummer65
Sider (fra-til)108923-108935
Antal sider13
ISSN1949-2553
DOI
StatusUdgivet - 12 dec. 2017
Eksternt udgivetJa

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