Genomic deletion of chromosome 12p is an independent prognostic marker in prostate cancer
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Genomic deletion of chromosome 12p is an independent prognostic marker in prostate cancer. / Kluth, Martina; Ahrary, Ramin; Hube-Magg, Claudia; Ahmed, Malik; Volta, Heike; Schwemin, C.; Steurer, Stefan; Wittmer, Corinna; Wilczak, Waldemar; Burandt, Eike; Krech, Till; Adam, Meike; Michl, Uwe; Heinzer, Hans; Salomon, Georg; Graefen, Markus; Koop, Christina; Minner, Sarah; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten.
in: ONCOTARGET, Jahrgang 6, Nr. 29, 29.09.2015, S. 27966-79.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Genomic deletion of chromosome 12p is an independent prognostic marker in prostate cancer
AU - Kluth, Martina
AU - Ahrary, Ramin
AU - Hube-Magg, Claudia
AU - Ahmed, Malik
AU - Volta, Heike
AU - Schwemin, C.
AU - Steurer, Stefan
AU - Wittmer, Corinna
AU - Wilczak, Waldemar
AU - Burandt, Eike
AU - Krech, Till
AU - Adam, Meike
AU - Michl, Uwe
AU - Heinzer, Hans
AU - Salomon, Georg
AU - Graefen, Markus
AU - Koop, Christina
AU - Minner, Sarah
AU - Simon, Ronald
AU - Sauter, Guido
AU - Schlomm, Thorsten
PY - 2015/9/29
Y1 - 2015/9/29
N2 - Deletion of 12p is a recurrent alteration in prostate cancer, but the prevalence and clinical consequences of this alteration have not been studied in detail. Dual labeling fluorescence in situ hybridization using probes for 12p13 (CDKN1B; p27) and centromere 12 as a reference was used to successfully analyze more than 3700 prostate cancers with clinical follow-up data assembled in a tissue microarray format. CDKN1B was selected as a probe because it is located in the center of the deletion, which spans > 10 Mb and includes > 50 genes in 80% of cancers with 12p deletion. Deletion of 12p was found in 13.7% of cancers and included 13.5% heterozygous and 0.2% homozygous deletions. 12p deletion were linked to advanced tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), rapid tumor cell proliferation (p < 0.0001), lymph node metastasis (p = 0.0004), and biochemical recurrence (p = 0.0027). Multivariate analysis including pT stage (p < 0.0001), Gleason grade (p < 0.0001), pN status (p = 0.0001), preoperative PSA levels (p = 0.0001), and resection margin status (p = 0.0001) revealed an independent prognostic value of 12p deletion (p = 0.0014). Deletion of 12p was unrelated to the ERG fusion status. Deletion of 12p was only marginally linked to reduced p27 expression, which by itself was unrelated to clinical outcome. This argues against p27 as the key target gene of 12p deletions. In summary, the results of our study demonstrate that 12p deletion is frequent in prostate cancer and provides independent prognostic information. 12p deletion analysis alone, or in combination with other prognostic parameters may thus have clinical utility.
AB - Deletion of 12p is a recurrent alteration in prostate cancer, but the prevalence and clinical consequences of this alteration have not been studied in detail. Dual labeling fluorescence in situ hybridization using probes for 12p13 (CDKN1B; p27) and centromere 12 as a reference was used to successfully analyze more than 3700 prostate cancers with clinical follow-up data assembled in a tissue microarray format. CDKN1B was selected as a probe because it is located in the center of the deletion, which spans > 10 Mb and includes > 50 genes in 80% of cancers with 12p deletion. Deletion of 12p was found in 13.7% of cancers and included 13.5% heterozygous and 0.2% homozygous deletions. 12p deletion were linked to advanced tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), rapid tumor cell proliferation (p < 0.0001), lymph node metastasis (p = 0.0004), and biochemical recurrence (p = 0.0027). Multivariate analysis including pT stage (p < 0.0001), Gleason grade (p < 0.0001), pN status (p = 0.0001), preoperative PSA levels (p = 0.0001), and resection margin status (p = 0.0001) revealed an independent prognostic value of 12p deletion (p = 0.0014). Deletion of 12p was unrelated to the ERG fusion status. Deletion of 12p was only marginally linked to reduced p27 expression, which by itself was unrelated to clinical outcome. This argues against p27 as the key target gene of 12p deletions. In summary, the results of our study demonstrate that 12p deletion is frequent in prostate cancer and provides independent prognostic information. 12p deletion analysis alone, or in combination with other prognostic parameters may thus have clinical utility.
U2 - 10.18632/oncotarget.4626
DO - 10.18632/oncotarget.4626
M3 - SCORING: Journal article
C2 - 26293672
VL - 6
SP - 27966
EP - 27979
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 29
ER -
