Promoter hypermethylation profile of kidney cancer with new proapoptotic p53 target genes and clinical implications.
Standard
Promoter hypermethylation profile of kidney cancer with new proapoptotic p53 target genes and clinical implications. / Christoph, Frank; Weikert, Steffen; Kempkensteffen, Carsten; Krause, Hans; Schostak, Martin; Köllermann, Jens; Miller, Kurt; Schrader, Mark.
in: CLIN CANCER RES, Jahrgang 12, Nr. 17, 17, 2006, S. 5040-5046.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Promoter hypermethylation profile of kidney cancer with new proapoptotic p53 target genes and clinical implications.
AU - Christoph, Frank
AU - Weikert, Steffen
AU - Kempkensteffen, Carsten
AU - Krause, Hans
AU - Schostak, Martin
AU - Köllermann, Jens
AU - Miller, Kurt
AU - Schrader, Mark
PY - 2006
Y1 - 2006
N2 - PURPOSE: Risk stratification of renal cell carcinoma is based on the histopathologic classification. Promoter hypermethylation as a mechanism of gene inactivation in renal cell carcinoma has been shown for only a small number of genes. We examined the usefulness of quantitative methylation analysis with a new set of p53 target genes for determining the clinical outcome and aggressiveness of the tumor disease. EXPERIMENTAL DESIGN: The genes selected were APAF-1, CASPASE-8, DAPK-1, IGFBP-3, and PML. The tissue samples analyzed were taken from tumor specimens obtained from 90 consecutive patients with clear cell renal carcinoma and from 20 normal kidney specimens. Quantitative methylation analysis of CpG sites in the promoter region was done by methylation-specific real-time PCR and the normalized index of methylation (NIM) was determined for each sample. RESULTS: Hypermethylation of the promoter region was common for APAF-1 (97%) and DAPK-1 (41%) but not for IGFBP-3 (3%), PML (3%), or CASP-8 (0%). The tumor patients had a median follow-up of 55 months. A correlation was found between the methylation level of APAF-1 and tumor size and nodal status, but not for tumor stage, grade, and age of patient. Kaplan-Meier analysis was able to identify patients with a higher risk of recurrence and tumor-related death by using APAF-1 (>or=56% NIM) and DAPK-1 (>or=10% NIM) methylation levels. In multivariate analysis, APAF-1 and DAPK-1 methylation levels were independent prognostic markers for metastatic disease and death from renal cell carcinoma. CONCLUSIONS: Our findings indicate that promoter hypermethylation of APAF-1 and DAPK-1 is a marker of aggressive renal cell carcinoma and provides independent prognostic information on disease outcome.
AB - PURPOSE: Risk stratification of renal cell carcinoma is based on the histopathologic classification. Promoter hypermethylation as a mechanism of gene inactivation in renal cell carcinoma has been shown for only a small number of genes. We examined the usefulness of quantitative methylation analysis with a new set of p53 target genes for determining the clinical outcome and aggressiveness of the tumor disease. EXPERIMENTAL DESIGN: The genes selected were APAF-1, CASPASE-8, DAPK-1, IGFBP-3, and PML. The tissue samples analyzed were taken from tumor specimens obtained from 90 consecutive patients with clear cell renal carcinoma and from 20 normal kidney specimens. Quantitative methylation analysis of CpG sites in the promoter region was done by methylation-specific real-time PCR and the normalized index of methylation (NIM) was determined for each sample. RESULTS: Hypermethylation of the promoter region was common for APAF-1 (97%) and DAPK-1 (41%) but not for IGFBP-3 (3%), PML (3%), or CASP-8 (0%). The tumor patients had a median follow-up of 55 months. A correlation was found between the methylation level of APAF-1 and tumor size and nodal status, but not for tumor stage, grade, and age of patient. Kaplan-Meier analysis was able to identify patients with a higher risk of recurrence and tumor-related death by using APAF-1 (>or=56% NIM) and DAPK-1 (>or=10% NIM) methylation levels. In multivariate analysis, APAF-1 and DAPK-1 methylation levels were independent prognostic markers for metastatic disease and death from renal cell carcinoma. CONCLUSIONS: Our findings indicate that promoter hypermethylation of APAF-1 and DAPK-1 is a marker of aggressive renal cell carcinoma and provides independent prognostic information on disease outcome.
M3 - SCORING: Zeitschriftenaufsatz
VL - 12
SP - 5040
EP - 5046
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 17
M1 - 17
ER -