Chromosome 5 harbors two independent deletion hotspots at 5q13 and 5q21 that characterize biologically different subsets of aggressive prostate cancer

TY - JOUR

T1 - Chromosome 5 harbors two independent deletion hotspots at 5q13 and 5q21 that characterize biologically different subsets of aggressive prostate cancer

AU - Möller, Katharina

AU - Kluth, Martina

AU - Ahmed, Malik

AU - Burkhardt, Lia

AU - Möller-Koop, Christina

AU - Büscheck, Franziska

AU - Weidemann, Sören

AU - Tsourlakis, Maria-Christina

AU - Minner, Sarah

AU - Heinzer, Hans

AU - Huland, Hartwig

AU - Graefen, Markus

AU - Sauter, Guido

AU - Schlomm, Thorsten

AU - Dum, David

AU - Simon, Ronald

N1 - © 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of Union for International Cancer Control.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - Deletion of chromosome 5q is common in prostate cancer and is linked to aggressive disease. Most previous studies focused on 5q21 where CHD1 is located, but deletion of mapping studies has identified a second deletion hotspot at 5q13. To clarify the prevalence and clinical relevance of 5q13 deletions and to determine the relative importance of 5q13 and 5q21 abnormalities, a tissue microarray containing samples from 12 427 prostate cancers was analyzed by fluorescence in situ hybridization. Deletion of 5q13 and 5q21 was found in 13.5% and 10%, respectively, of 7932 successfully analyzed cancers. Deletion was restricted to 5q13 in 49.4% and to 5q21 in 32.0% of cancers with a 5q deletion. Only 18.6% of 5q-deleted cancers had deletions of both loci. Both 5q13 and 5q21 deletions were significantly linked to advanced tumor stage, high Gleason grade, nodal metastasis and early biochemical recurrence (P < .005 each). Cancers with co-deletion of 5q13 and 5q21 had a worse prognosis than cancers with isolated 5q13 or 5q21 deletion (P = .0080). Comparison with TMPRSS2:ERG fusion status revealed that 5q21 deletions were tightly linked to ERG negativity (P < .0001) while 5q13 deletions were unrelated to the ERG status. In summary, 5q13 deletion and 5q21 deletion are common, but independent genomic alterations with different functional effects lead to aggressive prostate cancer.

AB - Deletion of chromosome 5q is common in prostate cancer and is linked to aggressive disease. Most previous studies focused on 5q21 where CHD1 is located, but deletion of mapping studies has identified a second deletion hotspot at 5q13. To clarify the prevalence and clinical relevance of 5q13 deletions and to determine the relative importance of 5q13 and 5q21 abnormalities, a tissue microarray containing samples from 12 427 prostate cancers was analyzed by fluorescence in situ hybridization. Deletion of 5q13 and 5q21 was found in 13.5% and 10%, respectively, of 7932 successfully analyzed cancers. Deletion was restricted to 5q13 in 49.4% and to 5q21 in 32.0% of cancers with a 5q deletion. Only 18.6% of 5q-deleted cancers had deletions of both loci. Both 5q13 and 5q21 deletions were significantly linked to advanced tumor stage, high Gleason grade, nodal metastasis and early biochemical recurrence (P < .005 each). Cancers with co-deletion of 5q13 and 5q21 had a worse prognosis than cancers with isolated 5q13 or 5q21 deletion (P = .0080). Comparison with TMPRSS2:ERG fusion status revealed that 5q21 deletions were tightly linked to ERG negativity (P < .0001) while 5q13 deletions were unrelated to the ERG status. In summary, 5q13 deletion and 5q21 deletion are common, but independent genomic alterations with different functional effects lead to aggressive prostate cancer.

U2 - 10.1002/ijc.33344

DO - 10.1002/ijc.33344

M3 - SCORING: Journal article

C2 - 33045100

VL - 148

SP - 748

EP - 758

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 3

ER -