8pter–p23 Deletion Is Associated with Racial Differences in Prostate Cancer Outcome

• Published in: Clinical cancer research Vol. 6; no. 12; pp. 4647 - 4652
• Main Authors: WASHBURN, Joseph G, WOJNO, Kirk J, DEY, Jyotirmoy, POWELL, Isaac J, MACOSKA, Jill A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2000
• Subjects: African Continental Ancestry Group; Aged; Alleles; Biological and medical sciences; Chromosome Deletion; Chromosomes, Human, Pair 8; Disease-Free Survival; European Continental Ancestry Group; Humans; Loss of Heterozygosity; Male; Medical sciences; Microsatellite Repeats; Middle Aged; Nephrology. Urinary tract diseases; Prognosis; Proportional Hazards Models; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms - ethnology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Risk Factors; Time Factors; Treatment Outcome; Tumors of the urinary system; Urinary tract. Prostate gland; Eastern Europe; Europe; Caucasus; Human; Short arm; Urinary system disease; Prognosis; Genetic variability; Prostate disease; American; Nucleotide sequence; Tumoral tissue; Malignant tumor; In vitro; Survival; African; Chromosome 8; Interindividual comparison; Race; Deletion; Predictive factor; Male genital diseases; Prostate
• ISSN: 1078-0432; 1557-3265

Deletions of chromosome sequences mapping to the short arm of chromosome 8 have been observed frequently in a variety of human cancers. A small number of studies have suggested that the terminal portion of the short arm of chromosome 8, 8pter–p23, may be deleted independently of other portions of 8p in human tumors, and that deletion of the 8pter–p23 region may be correlated with poor prognosis. The aim of the present study was to physically define the minimal region of 8pter–p23 deletion and to define the frequency and prognostic significance of 8pter–p23 loss in human prostate tumors. DNA was purified from normal and tumor tissues of 45 radical prostatectomy specimens and amplified for 15 highly polymorphic microsatellite sequences, 13 spanning 8pter–p23 and 2 proximal 8p markers. Allelic loss of 8p sequences was observed in 28 of 45 (62%) tumors examined. Of these, approximately half (12 of 28; 43%) demonstrated independent loss of the 8pter–p23 region, with several tumors defining a 5-cM minimal region of deletion spanning D8S264-D8S1824-D8S1781-D8S262-D8S1798 . When serum prostate-specific antigen was used as a surrogate end point marker for survival, 8pter–p23 loss was significantly associated with reduced disease-free progression (log-rank P = 0.0426). Moreover, loss of the 8pter–p23 region was significantly associated with poor survival for American Caucasian (log-rank P = 0.0024) but not African-American (log-rank P = 0.5832) prostate cancer patients. These studies suggest that independent deletion of 8pter–p23 is differentially associated with disease recurrence and poor outcome in American Caucasian but not African-American prostate cancer patients.