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Genetic markers associated with early cancer‐specific mortality following prostatectomy
Cancer, 2013-07, Vol.119 (13), p.2405-2412
Liu, Wennuan
Xie, Chunmei C.
Thomas, Christopher Y.
Kim, Seong‐Tae
Lindberg, Johan
Egevad, Lars
Wang, Zhong
Zhang, Zheng
Sun, Jishan
Sun, Jielin
Koty, Patrick P.
Kader, A. Karim
Cramer, Scott D.
Bova, G. Steven
Zheng, S. Lilly
Grönberg, Henrik
Isaacs, William B.
Xu, Jianfeng
2013
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Liu, Wennuan
Xie, Chunmei C.
Thomas, Christopher Y.
Kim, Seong‐Tae
Lindberg, Johan
Egevad, Lars
Wang, Zhong
Zhang, Zheng
Sun, Jishan
Sun, Jielin
Koty, Patrick P.
Kader, A. Karim
Cramer, Scott D.
Bova, G. Steven
Zheng, S. Lilly
Grönberg, Henrik
Isaacs, William B.
Xu, Jianfeng
Titel
Genetic markers associated with early cancer‐specific mortality following prostatectomy
Ist Teil von
Cancer, 2013-07, Vol.119 (13), p.2405-2412
Ort / Verlag
Hoboken, NJ: Wiley-Blackwell
Erscheinungsjahr
2013
Quelle
MEDLINE
Beschreibungen/Notizen
BACKGROUND This study sought to identify novel effectors and markers of localized but potentially life‐threatening prostate cancer (PCa), by evaluating chromosomal copy number alterations (CNAs) in tumors from patients who underwent prostatectomy and correlating these with clinicopathologic features and outcome. METHODS CNAs in tumor DNA samples from 125 patients in the discovery cohort who underwent prostatectomy were assayed with high‐resolution Affymetrix 6.0 single‐nucleotide polymorphism microarrays and then analyzed using the Genomic Identification of Significant Targets in Cancer (GISTIC) algorithm. RESULTS The assays revealed 20 significant regions of CNAs, 4 of them novel, and identified the target genes of 4 of the alterations. By univariate analysis, 7 CNAs were significantly associated with early PCa‐specific mortality. These included gains of chromosomal regions that contain the genes MYC, ADAR, or TPD52 and losses of sequences that incorporate SERPINB5, USP10, PTEN, or TP53. On multivariate analysis, only the CNAs of PTEN (phosphatase and tensin homolog) and MYC (v‐myc myelocytomatosis viral oncogene homolog) contributed additional prognostic information independent of that provided by pathologic stage, Gleason score, and initial prostate‐specific antigen level. Patients whose tumors had alterations of both genes had a markedly elevated risk of PCa‐specific mortality (odds ratio = 53; 95% CI = 6.92‐405, P = 1 × 10−4). Analyses of 333 tumors from 3 additional distinct patient cohorts confirmed the relationship between CNAs of PTEN and MYC and lethal PCa. CONCLUSIONS This study identified new CNAs and genes that likely contribute to the pathogenesis of localized PCa and suggests that patients whose tumors have acquired CNAs of PTEN, MYC, or both have an increased risk of early PCa‐specific mortality. Cancer 2013;119:2405‐2412. © 2013 American Cancer Society. Genome‐wide analysis of prostate cancer reveals copy number alterations of multiple genetic loci associated with early cancer‐specific mortality. These findings may allow for more accurate patient prognosis at the time of surgery or biopsy, and may help guide the selection of appropriate therapy.
Sprache
Englisch
Identifikatoren
ISSN: 0008-543X, 1097-0142
eISSN: 1097-0142
DOI: 10.1002/cncr.27954
Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_126892351
Format
–
Schlagworte
Adult
,
Aged
,
Biological and medical sciences
,
DNA Copy Number Variations
,
Genetic Markers
,
Humans
,
Male
,
Medical sciences
,
Medicin och hälsovetenskap
,
Middle Aged
,
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
,
MYC
,
Neoplasm Grading
,
Neoplasm Staging
,
Nephrology. Urinary tract diseases
,
Odds Ratio
,
Polymorphism, Single Nucleotide
,
Predictive Value of Tests
,
Prognosis
,
prostate cancer death
,
Prostate-Specific Antigen - blood
,
Prostatectomy
,
Prostatic Neoplasms - blood
,
Prostatic Neoplasms - genetics
,
Prostatic Neoplasms - mortality
,
Prostatic Neoplasms - pathology
,
Prostatic Neoplasms - surgery
,
Proto-Oncogenes - genetics
,
PTEN
,
somatic DNA copy number
,
Tumors
,
Tumors of the urinary system
,
Urinary tract. Prostate gland
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