TY - JOUR

T1 - Deletion lengthening at chromosomes 6q and 16q targets multiple tumor suppressor genes and is associated with an increasingly poor prognosis in prostate cancer

AU - Kluth, Martina

AU - Jung, Simon

AU - Habib, Omar

AU - Eshagzaiy, Mina

AU - Heinl, Anna

AU - Amschler, Nina

AU - Masser, Sawinee

AU - Mader, Malte

AU - Runte, Frederic

AU - Barow, Philipp

AU - Frogh, Sohall

AU - Omari, Jazan

AU - Möller-Koop, Christina

AU - Hube-Magg, Claudia

AU - Weischenfeldt, Joachim

AU - Korbel, Jan

AU - Steurer, Stefan

AU - Krech, Till

AU - Huland, Hartwig

AU - Graefen, Markus

AU - Minner, Sarah

AU - Sauter, Guido

AU - Schlomm, Thorsten

AU - Simon, Ronald

PY - 2017/12/12

Y1 - 2017/12/12

N2 - 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.

AB - 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.

U2 - 10.18632/oncotarget.22408

DO - 10.18632/oncotarget.22408

M3 - Journal article

C2 - 29312579

VL - 8

SP - 108923

EP - 108935

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 65

ER -