5q21 deletion is often heterogeneous in prostate cancer

TY - JOUR

T1 - 5q21 deletion is often heterogeneous in prostate cancer

AU - Kluth, Martina

AU - Al Kilani, Zaid

AU - Özden, Cansu

AU - Hussein, Khakan

AU - Frogh, Sohall

AU - Möller-Koop, Christina

AU - Burandt, Eike

AU - Steurer, Stefan

AU - Büscheck, Franziska

AU - Jacobsen, Frank

AU - Luebke, Andreas M

AU - Minner, Sarah

AU - Tsourlakis, Maria Christina

AU - Hoeflmayer, Doris

AU - Wittmer, Corinna

AU - Schlomm, Thorsten

AU - Sauter, Guido

AU - Simon, Ronald

AU - Wilczak, Waldemar

N1 - © 2019 Wiley Periodicals, Inc.

PY - 2019/8

Y1 - 2019/8

N2 - Cancer heterogeneity represents a challenge for the analysis of prognostic molecular markers but can be used to study the evolution of molecular events in tumors. To assess the degree of heterogeneity of 5q21 deletions and their relationship with TMPRSS2:ERG status and 6q15 deletions in prostate cancer, a heterogeneity tissue microarray including 10 tissue spots from 10 different areas of 317 cancers was analyzed by fluorescence in situ hybridization for 5q21 deletion. Data on 6q and ERG were available from earlier studies. Deletions of 5q21 were found in 23% of 265 interpretable cancers and showed marked intratumoral heterogeneity. In the subset of 246 cancers with at least 3 interpretable spots, 23% had a 5q21 deletion. Heterogeneous 5q21 deletions were found in 71% and homogeneous in 29% of these cancers. The likelihood of 5q21 deletion was twice as high in ERG-negative (28%) than in ERG-positive cancers (16%, P = .024). In all 21 cases harboring both alterations, the tumor area containing a 5q21 deletion was smaller or equally large than the ERG-positive area but never larger. Deletions of 5q and 6q were significantly linked. However, the analysis of 32 tumors harboring both deletions did not suggest a specific order of appearance of these deletions. The 5q21 deletion preceded 6q15 in 10 tumors and 6q15 preceded 5q21 in 14 tumors. In summary, our study identifies 5q21 deletion as a highly heterogeneous aberration in prostate cancer that usually occurs late during cancer progression. This is a severe limitation for using 5q21 testing as a prognostic tool.

AB - Cancer heterogeneity represents a challenge for the analysis of prognostic molecular markers but can be used to study the evolution of molecular events in tumors. To assess the degree of heterogeneity of 5q21 deletions and their relationship with TMPRSS2:ERG status and 6q15 deletions in prostate cancer, a heterogeneity tissue microarray including 10 tissue spots from 10 different areas of 317 cancers was analyzed by fluorescence in situ hybridization for 5q21 deletion. Data on 6q and ERG were available from earlier studies. Deletions of 5q21 were found in 23% of 265 interpretable cancers and showed marked intratumoral heterogeneity. In the subset of 246 cancers with at least 3 interpretable spots, 23% had a 5q21 deletion. Heterogeneous 5q21 deletions were found in 71% and homogeneous in 29% of these cancers. The likelihood of 5q21 deletion was twice as high in ERG-negative (28%) than in ERG-positive cancers (16%, P = .024). In all 21 cases harboring both alterations, the tumor area containing a 5q21 deletion was smaller or equally large than the ERG-positive area but never larger. Deletions of 5q and 6q were significantly linked. However, the analysis of 32 tumors harboring both deletions did not suggest a specific order of appearance of these deletions. The 5q21 deletion preceded 6q15 in 10 tumors and 6q15 preceded 5q21 in 14 tumors. In summary, our study identifies 5q21 deletion as a highly heterogeneous aberration in prostate cancer that usually occurs late during cancer progression. This is a severe limitation for using 5q21 testing as a prognostic tool.

U2 - 10.1002/gcc.22730

DO - 10.1002/gcc.22730

M3 - SCORING: Journal article

C2 - 30623509

VL - 58

SP - 509

EP - 515

JO - GENE CHROMOSOME CANC

JF - GENE CHROMOSOME CANC

SN - 1045-2257

IS - 8

ER -