Loss of chromosome arm 8p loci in prostate cancer: Mapping by quantitative allelic imbalance

Abstract

A previous study of 18 primary or metastatic prostate cancers showed loss of genetic markers on chromosome 8; 10, or 16 in more than 50% of cases [Bergerheim USR et al. (1991) Genes Chromosom Cancer 3:215-220]. The small size and infiltrative nature of primary prostatic tumors have hindered efforts to assess allelic losses by traditional restriction fragment length polymorphism (RFLP)/Southern blotting methods. To improve the sensitivity and specificity of this analysis in early prostate cancer, we have amplified polymorphic microsatellite repeats by polymerase chain reaction (PCR), and have quantitated allelic imbalances with phosphor imaging technology. In this study, 63 primary prostate tumors and matched benign tissues obtained by radical prostatectomy were examined at 28 genetic loci on chromosome 8, all but five of which were located on the short arm. Twenty-nine (46%) of the 63 cases showed loss of at least one locus. Multiple adjacent loci, usually including the LPL and MSR genes in 8p22, were lost in 28 cases. In 10 of these, losses were observed at all informative loci on the p arm. In another 15 tumors, losses were restricted to subregions of the p arm by loci retained either distally toward the p terminus or proximally at the 8p12-8p21 border, or both. In three tumors, two discrete regions of loss were observed within 8p, separated by several retained loci. Allelic loss of 8p loci was associated with higher tumor grade. These data are complementary to previous reports of allelic deletions in colorectal, hepatocellular, and non-small cell lung cancers and suggest the existence of one or more pleotropic tumor suppressor genes on 8p.

Molecular analysis of the FHIT gene in human prostate cancer

“…The procedure which followed is described above (see Quantitative FHIT transcript analysis). Allelic imbalance was considered to be present when the relative intensity of the two alleles in tumor DNA di ered from the relative intensity in lymphocyte DNA by a factor of at least 1.5; this is a validated cut-o value to determine AI of microsatellite loci in tumor samples containing 460% cancer cells (McGrogan et al, 1994). Each analysis was performed at least twice to ensure reproducible detection of AI (repeat independent PCR ampli®cation, gel separation, and quanti®cation).…”

Localization of a putative tumor suppressor gene in the sub-telomeric region of chromosome 8p

“…A growing body of evidence suggests that there are several tumor suppressor genes on the short arm of chromosome 8 (8p) and that these genes are inactivated in a variety of human malignancies (Fujiwara et al, 1993;Macgrogan et al, 1994;Yaremko et al, 1994). These putative suppressors, however, have yet to be cloned.…”

Allelic imbalance and biochemical outcome after radical prostatectomy

“…At least two distinct regions of loss have been reported. 51,52 Loss of 8p12-21 is an early event in prostate carcinogenesis, occurring in HGPIN and early invasive disease, whereas loss of 8p22 is a late event, found more commonly in advanced cancers. 53 Marker D8S136 on 8p12-22 demonstrated AI in 39% of informative patients, marker NEFL at 8p21.3 in 62% and marker D8S1991 at 8p22 in 47%.…”