Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancers

Abstract

Human prostate cancers frequently show loss of heterozygosity (LOH) at loci on the long arm of chromosome 16 (16q). In this study, we analyzed prostate cancer specimens from 48 patients (Stage B, 20 cases; Stage C, 10 cases; cancer death, 18 cases) for allelic loss on 16q, using either restriction fragment length polymorphism (RFLP)‐ or polymerase chain reaction (PCR)‐based methods. Allelic losses were observed in 20 (42%) of 48 cases, all of which were informative with at least one locus. Detailed deletion mapping identified three distinct commonly deleted regions on this chromosome arm: q22.1–q22.3, q23.2–q24.1, and q24.3‐qter. On the basis of a published sex‐averaged framework map, the estimated sizes of the commonly deleted regions were 4.7 (16q22.1–q22.3), 17.2 (16q23.2–q24.1) and 8.4 cM (16q24.3‐qter). Allelic losses on 16q were observed more frequently in the cancer‐death cases (11 of 18; 61%) than in early‐stage tumor cases (9 of 30; 30%; P < 0.05). In 7 of 11 patients from whom DNA was available from metastatic cancers as well as from normal tissues and primary tumors, the primary cancer foci had no detectable abnormality of 16q, but the metastatic tumors showed LOH. These results suggest that inactivation of tumor suppressor genes on 16q plays an important role in the progression of prostate cancer. We also analyzed exons 5–8 of the E‐cadherin gene, located at 16q22.1, in tumor DNA by means of PCR‐single strand conformation polymorphism and direct sequencing, but we detected no somatic mutations in this candidate gene. Genes Chromosom Cancer 17:225–233 (1996). © 1996 Wiley‐Liss, Inc.

Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors

“…The region of LOH in 16q23.2-24.1 showed higher frequencies of alteration in distant metastases of breast and prostate cancers (Suzuki et al, 1996;Li et al, 1999). Furthermore, it has been shown by microcell-mediated chromosome transfer that chromosome 16q23-24 is a strong suppressor of the metastatic activity of a prostatic cancer cell line (Mashimo et al, 1998).…”

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

“…[4][5][6] We have investigated several regions of chromosomal loss in prostate cancer using LOH analysis. [7][8][9][10][11][12][13][14][15] CGH is a molecular technique that allows screening of the whole genome for DNA sequence copy number alterations. Regions of increased copy number may contain oncogenes, whereas regions of decreased copy number may contain putative TSGs.…”

Allelic imbalance and biochemical outcome after radical prostatectomy

“…Allelic imbalance at one or more loci was seen in 57 (92%) of the 62 patients. Five patients who did not show AI, three men in the relapse group (24,25,64) and two in the non-relapse group (30, 61) ( Table 3).…”

“…19 Some losses, such as those on 8p and 13q, are associated with early prostate cancer. 11,12,22,23 Others, such as those on 11p and 16q, 15,[20][21][22]24 are more frequent in advanced disease. Several studies have reported an association of AI at certain loci with histopathological features of the RP specimen, including advanced stage, 13,[25][26][27] high Gleason grade 13,26 and perineural invasion.…”