1.
Aitchison AA, Veerakumarasivam A, Vias M, Kumar R, Hamdy FC, Neal DE, Mills IG.
Prostate. 2008 May 1;68(6):661-74. doi: 10.1002/pros.20730.
- PMID:
- 18213629
2.
Yamamoto F, Yamamoto M.
Electrophoresis. 2007 Jun;28(12):1882-95.
Abstract
We
examined differences in copy number and expression of 127 genes located
on the 18q21-qter chromosomal region of the breast and prostate cancer
cell lines, using the systematic multiplex PCR and reverse
transcription-PCR (SM PCR and SM RT-PCR) methods that we developed.
Semi-quantitative data were obtained that were comparable in quality,
but not in quantity, to data from DNA microarray hybridization analysis.
In the chromosomal region where losses are frequent in breast,
prostate, and other cancers, we detected a homozygous deletion of the
SMAD4 gene in the MDA-MB-468 breast cancer cell line. We also observed partial or entire loss
of expression in genes such as CCBE1, CCDC11, CD226, NP_115536.1,
NP_689683.2, RNF152, SERPINB8, and TCF4 in certain breast and/or
prostate cancer cell lines. An increase in gene expression was rare, but found with the transcription factor ONECUT2 gene in all of the cancer
cell lines examined. Real-time qRT-PCR experiments confirmed these SM
RT-PCR results. Further analysis of clinical specimens of breast cancer
by real-time qRT-PCR demonstrated that the gene expression of CCBE1,
TCF4, NP_115536.1, and NP_689683.2 was downregulated in the majority of
clinical cases of breast cancer.
3.
Chaudhary J, Schmidt M.
Chromosome Res. 2006;14(5):567-86. Epub 2006 Jul 12.
- PMID:
- 16823619
4.
Gagnon A, Ripeau JS, Zvieriev V, Chevrette M.
Genes Chromosomes Cancer. 2006 Mar;45(3):220-30.
- PMID:
- 16281261
5.
Padalecki
SS, Weldon KS, Reveles XT, Buller CL, Grubbs B, Cui Y, Yin JJ, Hall DC,
Hummer BT, Weissman BE, Dallas M, Guise TA, Leach RJ, Johnson-Pais TL.
Urol Oncol. 2003 Sep-Oct;21(5):366-73.
Abstract
Although prostate cancer is still the most diagnosed cancer
in men, most genes implicated in its progression are yet to be
identified. Chromosome abnormalities have been detected in human
prostate tumors, many of them associated with prostate cancer
progression. Indeed, alterations (including deletions or
amplifications) of more than 15 human chromosomes have been reported in
prostate cancer. We hypothesized that transferring normal human chromosomes into human prostate cancer
cells would interfere with their tumorigenic and/or metastatic
properties. We used microcell-mediated chromosome transfer to introduce
human chromosomes 10, 12, 17, and 18 into highly tumorigenic
(PC-3M-Pro4) and highly metastatic (PC-3M-LN4) PC-3-derived cell lines.
We tested the in vitro and in vivo properties of these hybrids.
Introducing chromosome 18 into the PC-3M-LN4 prostate cancer
cell line greatly reduced its tumorigenic phenotype. We observed
retarded growth in soft agar, decreased invasiveness through Matrigel,
and delayed tumor growth into nude mice, both subcutaneously and
orthotopically. This phenotype is associated with a marker in the 18q21
region. Combined with the loss of human chromosome 18 regions often seen in patients with advanced prostate cancer, our results show that chromosome 18 encodes one or more tumor-suppressor genes whose inactivation contributes to prostate cancer progression.
6.
Yin Z, Babaian RJ, Troncoso P, Strom SS, Spitz MR, Caudell JJ, Stein JD, Kagan J.
Oncogene. 2001 Apr 26;20(18):2273-80.
- PMID:
- 11402322
7.
Fu W, Bubendorf L, Willi N, Moch H, Mihatsch MJ, Sauter G, Gasser TC.
Urology. 2000 Nov 1;56(5):880-5.
Abstract
OBJECTIVES:
The genetic basis underlying prostate cancer development and progression is poorly understood. The primary aim of this study was to identify chromosomal regions important for progression in clinically localized prostate cancer removed by radical prostatectomy.METHODS:
Comparative genomic hybridization was used for whole genome screening of DNA sequence copy number alterations in 28 pathologically organ-confined tumors (pT2) and 28 tumors with infiltration of the seminal vesicles (pT3b).RESULTS:
Comparative genomic hybridization analysis showed on average 2.0 +/- 2.4 chromosomal alterations per tumor with more frequent losses (mean 1.3 +/- 1.8) than gains (mean 0.7 +/- 1.0). The percentage of tumors without alterations was higher in Stage pT2 (21%) than in Stage pT3b (50%). Losses of 8p (21%), 13q (21%), 5q (14%), 16q (14%), and 18q (13%) and gains of Xq (21%) and 8q (9%) were the most prevalent changes. Distinct regional alterations included minimal overlapping regions of loss at 5q13-q21, 6q14-q21, and 18q21-qter. There was only a small increase in the number of alterations from Stage pT2 to Stage pT3b (mean 1.6 +/- 2.3 versus 2.5 +/- 2.4). However, two individual alterations-gain of 8q and loss of 18q-were significantly more frequent in Stage pT3b than in Stage pT2 prostate cancer (P = 0.02 and P = 0.04, respectively), suggesting that genes in these regions may be important for prostate cancer progression.CONCLUSIONS:
The detection of chromosome 8q gains and 18q losses and the identification of the corresponding target genes could become a molecular tool for better characterization of clinically localized prostate cancer.
8.
Padalecki SS, Troyer DA, Hansen MF, Saric T, Schneider BG, O'Connell P, Leach RJ.
Int J Cancer. 2000 Mar 1;85(5):654-8.
Abstract
Like most cancers, prostate cancer
(CaP) is believed to be the result of the accumulation of genetic
alterations within cells. Previous studies have implicated numerous
chromosomal regions with elevated rates of allelic imbalance (AI), using
mostly primary CaPs with an unknown disease outcome. These regions of
AI are proposed sites for tumor suppressor genes. One of the regions
previously implicated as coding for at least one tumor suppressor gene
is the long arm of chromosome 18
(18q). To confirm this observation, as well as to narrow the critical
region for this putative tumor suppressor, we analyzed 32 metastatic CaP
specimens for AI on chromosome 18q. Thirty-one of these 32 specimens
(96.8%) exhibited AI at one or more loci on chromosome 18q. Our analysis
using 17 polymorphic markers revealed statistically significant AI on
chromosome 18q at 3 markers, D18S35, D18S64 and D18S461. Using these
markers as a guide, we have been able to identify 2 distinct minimum
regions of AI on 18q. The first region is between the genetic markers
D18S1119 and D18S64. The second region lies more distal on the long arm
of the chromosome and is between the genetic markers D18S848 and D18S58.
To determine if 18q loss is a late event in the progression of CaP, we also examined prostatic
intraepithelial neoplasia (PIN) and primary prostate tumors from 17
patients for AI with a subset of 18q markers. We found significantly
higher AI in the metastatic samples. Our results are consistent with 18q
losses occurring late in CaP progression.
9.
Latil A, Pesche S, Valéri A, Fournier G, Cussenot O, Lidereau R.
Prostate. 1999 Sep 1;40(4):225-31.
Abstract
BACKGROUND:
Loss of heterozygosity (LOH) on chromosome arm 18q is common in sporadic prostate cancer and may be involved in cancer development through inactivation of tumor-suppressor genes (TSG). Recent identification, at 18q21.1, of MADR2/Smad2, a key component in transforming growth factor beta (TGFbeta)-family signaling pathways, led us to investigate the role of this gene in prostate tumorigenesis.METHODS:
Sporadic primary prostate tumors from 25 patients with clinically localized tumors and 7 with metastatic forms were examined for MADR2/Smad2 mutations by using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis of cDNA, and for gene expression by quantitative reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:
We detected no mutation in MADR2/Smad2 and no abnormal mRNA expression.CONCLUSIONS:
Despite recent evidence indicating that MADR2/Smad2 acts as a tumor-suppressor gene, our findings suggest a limited role of this gene in prostate tumorigenesis, at least in the early stages. Another key tumor-suppressor gene may therefore be the main target of the observed LOH at 18q21.1.
Copyright 1999 Wiley-Liss, Inc.
10.
Rohrbach H, Haas CJ, Baretton GB, Hirschmann A, Diebold J, Behrendt RP, Löhrs U.
Prostate. 1999 Jun 15;40(1):20-7.
11.
Ueda T, Komiya A, Emi M, Suzuki H, Shiraishi T, Yatani R, Masai M, Yasuda K, Ito H.
Genes Chromosomes Cancer. 1997 Oct;20(2):140-7.
Abstract
We
analyzed normal/tumor DNA pairs obtained from 46 patients with prostate
cancers (stage B, 16 cases; C, 10 cases; D1, 4 cases; and endocrine
therapy-resistant cancer-death, 16 cases) for loss of heterozygosity using 32 microsatellite markers on chromosome 18. Seventeen of the 46 cases (37%) showed loss
of heterozygosity (LOH) for at least one locus on the long arm.
Detailed deletion mapping in these tumors identified a distinct commonly
deleted region within a 5-cM interval in 18q21.1. There was a
statistical correlation between the frequency of LOH on 18q and clinical
stage (chi 2 = 12.3; P = 0.0064). LOH on 18q was observed more
frequently in Stage D1 cases (4/4; 100%) than in stage B+C cases (5/26;
19%; P = 0.0046, Fisher's exact test). In 8 of 9 (89%) cancer-death
patients from whom DNAs were available from both primary and metastatic
tumors, the primary tumors had either no detectable abnormality of chromosome 18 or the region involving loss
of heterozygosity was limited while the metastatic foci showed more
frequent and extended allelic losses on this chromosome. No
abnormalities were detected in the DCC and DPC4 genes when their exons
were analyzed separately by single strand conformation polymorphism
assay. These results suggest that inactivation of one or more putative
tumor suppressor genes on 18q21 other than DCC and DPC4 plays an
important role in the progression of human prostate cancer.
- PMID:
- 9331564
- [Indexed for MEDLINE]
12.
MacGrogan D, Pegram M, Slamon D, Bookstein R.
Oncogene. 1997 Aug 28;15(9):1111-4.
Abstract
Allelic
deletions of chromosome 18q are reported to be common in prostate and
colorectal cancers, suggesting that one or more tumor suppressor genes
on 18q are involved in the genesis of these neoplasms. The DPC4 gene, a recently identified candidate tumor suppressor in 18q21, was examined for evidence of inactivation in prostatic
carcinomas, and results compared to those of a parallel analysis of
colorectal carcinomas, for which DPC4 mutation has been reported in
approximately 10% of cases. In this study, only three (10%) of 29
informative primary prostate cancers showed allelic loss
of chromosome 18q21 markers, and no point mutations or deletions of
DPC4 were detected in the complete set of 45 primary or metastatic
cases. In contrast, five (56%) of nine primary colorectal tumors
displayed allelic loss
of 18q markers and in one of these a somatically acquired G-->T
missense mutation was found in exon 1. Of twelve colorectal tumor cell
lines, one showed a G-->C missense mutation in exon 8 and two had
partial homozygous deletions that would likely abrogate gene function.
These data suggest that DPC4 is rarely if ever mutated during prostatic oncogenesis, whereas inactivation of this gene may contribute to the genesis of a subset of colorectal carcinomas.
13.
Crundwell MC, Chughtai S, Knowles M, Takle L, Luscombe M, Neoptolemos JP, Morton DG, Phillips SM.
Int J Cancer. 1996 Aug 22;69(4):295-300.
Abstract
Previous studies have suggested the involvement of tumour-suppressor genes on chromosomes 8p, 22q and 18q (DCC) in prostate cancer.
The aim of this study was to further characterize these regions. We
investigated 20 polymorphic regions on the 3 chromosome arms in 43
cancers and 10 cases of benign prostatic hyperplasia (BPH). Allelic loss was observed in 72% of cancers on 8p, 16% on 22q and 24% at DCC. For BPH, loss
was observed in 20% on 8p and in 12% at DCC. The low incidence of LOH
on 22q implies that this locus has no significant role in prostate
carcinogenesis. At DCC, although the overall incidence was low, tumours
with LOH were mostly of high grade or had metastases, suggesting a role
for this gene in prostate cancer
progression. On chromosome 8p, 29% of cancers had deletions at the LPL
locus on 8p22 and 60% had deletions within a region flanked by the
markers D8S339 and ANKI on 8p 11.1-p21.1. Within this region, 2 distinct
areas of allelic loss
were observed, at one or both ANKI and D8S255, and in the region
defined by the markers D8S259-D8S505. For the regions 8p22 and
ANKI-D8S255, tumours with metastases had a greater frequency of LOH
compared to non-metastasizing tumours, suggesting the presence of
putative metastasis-suppressor genes in these regions.
14.
König JJ, Teubel W, Romijn JC, Schröder FH, Hagemeijer A.
Hum Pathol. 1996 Jul;27(7):720-7.
- PMID:
- 8698318
15.
Latil A, Baron JC, Cussenot O, Fournier G, Soussi T, Boccon-Gibod L, Le Duc A, Rouëssé J, Lidereau R.
Bull Cancer. 1995 Jul;82(7):589-97. French.
Prostate cancer
is one of the most common malignancies in men. Few authors have
attempted to identify consistent genetic alterations at the molecular
level in adenocarcinoma of the prostate, but those most frequently
reported are loss
of heterozygosity (LOH) involving chromosome arms 8p, 10q, 16q, and 18q
and inactivation of the TP53 tumor suppressor gene. In order to
determine if alterations frequently found in other adenocarcinomas
(breast, ovarian, colorectal), including losses of genetic material from
chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also
involved in prostate cancer,
we examined 20 localized early-stage prostate tumors. We detected no
mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p
(50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward
isolating tumor suppressor genes on 18q, we used six polymorphic markers
and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.
16.
König JJ, Teubel W, van Dongen JW, Romijn JC, Hagemeijer A, Schröder FH.
Prostate. 1994 Dec;25(6):281-91.
17.
Murty VV, Li RG, Houldsworth J, Bronson DL, Reuter VE, Bosl GJ, Chaganti RS.
Oncogene. 1994 Nov;9(11):3227-31.
Abstract
The
DCC tumor suppressor gene has been shown to be frequently deleted or
its expression reduced or absent in colorectal, gastro-intestinal,
pancreatic, prostatic,
and breast carcinomas, and glioblastomas. By allelotype analysis using
the DCC-flanking polymorphic marker D18S5 we have previously shown that
allelic deletions at 18q21 occur in 40% of male germ cell tumors (Murty
et al., 1994). In order to further understand the role of DCC gene in
germ cell tumorigenesis, we evaluated deletions by loss
of heterozygosity (LOH) and mRNA expression by RT-PCR in tumor tissues
and cell lines. Analysis of 61 paired normal-tumor DNAs using the probes
D18S5, JOSH 4.4 (a polymorphism within the DCC locus) and a (CA)n
polymorphism in an intron of DCC revealed that 45% of GCTs had allelic
deletions. In addition, two homozygous deletions were found in the DCC
gene among 91 (61 used in the LOH analysis and an additional 30) tumor
DNAs when screened with the cDNA probes (pDCC 1.65, pDCC 1.9 and pDCC
1.0). By RT-PCR analysis of four normal testes, nine GCT cell lines and
14 tumor tissues, DCC gene expression was detected in all four normal
testes, while four (45%) GCT cell lines and one (7%) tumor specimen
showed lack of expression. In addition, DCC expression was highly
reduced in three (21%) tumor tissues. The high frequency of LOH at 18q21
was characteristic of seminomas as well as all subsets of non-seminomas
in primary as well as metastatic states. Frequent allelic loss in all histologic subsets, homozygous deletions, and loss of expression of DCC suggest that suppression of this gene's function is an early event in GCT development.
18.
Massenkeil G, Oberhuber H, Hailemariam S, Sulser T, Diener PA, Bannwart F, Schäfer R, Schwarte-Waldhoff I.
Anticancer Res. 1994 Nov-Dec;14(6B):2785-90.
19.
Latil A, Baron JC, Cussenot O, Fournier G, Soussi T, Boccon-Gibod L, Le Duc A, Rouëssé J, Lidereau R.
Genes Chromosomes Cancer. 1994 Oct;11(2):119-25.
- PMID:
- 7529548
20.
Brewster SF, Browne S, Brown KW.
J Urol. 1994 Apr;151(4):1073-7.We present a restriction fragment length polymorphism (RFLP) analysis of 29 benign and 30 malignant prostatic
tumors, using polymorphic DNA probes to the putative tumor suppressor
genes DCC (Deleted in Colorectal Carcinoma; chromosome 18q21.3), nm23-H1
(17q21.3), APC (Adenomatous Polyposis Coli; 5q21) and p53 (17p13). Six
of 23 evaluable cancers (26%) showed loss
of heterozygosity (LOH) at DCC; 5 were advanced stage and one was
clinically localized (p < 0.05). Mapping 18q deletions, another
(advanced) cancer
showed LOH at a locus distal to DCC (18q22), but no LOH at DCC. Three
of 15 evaluable cancers (20%), all advanced, showed LOH at APC. Three of
eight (38%) cancers, of which 2 were advanced, showed LOH at p53. One
high grade/stage cancer
of 21 (5%) showed LOH at nm23-H1 (and also at DCC). Combining data,
allelic losses at either DCC, APC, or p53 genes were seen in 13% of
localized cancers, but in 71% of advanced cancers (p < 0.002).
Allelic loss involving nm23-H1 is rare in prostatic carcinoma. We suggest that loss
of tumor suppressor genes DCC and/or an unidentified gene located
distally on chromosome 18q, APC, or p53 may influence progression in prostatic carcinoma.
Similar articles
Genomics. 1991 Nov;11(3):530-6.
Allelotyping of human prostatic adenocarcinoma.
Abstract
Allelotyping
(using at least one probe detecting a restriction fragment length
polymorphism on each chromosomal arm, with the exception of the short
arms of the acrocentric chromosomes), showed loss
of genetic information in 11 of 18 prostate adenocarcinoma specimens
analyzed (61%). Frequent allelic deletions were detected on the long arm
of chromosome 16 (6 of 10 informative cases, 60%), on the short arm of
chromosome 8 (3 of 6 informative cases, 50%), and on the short and/or
the long arms of chromosome 10 (6 of 11 informative cases (10p), 55% and
4 of 13 informative cases (10q), 30%, respectively). No losses of
alleles were detected in any case unless at least one of the chromosomes
8, 10, or 16 also showed deletions. The long arm of chromosome 18
also showed a high frequency of allelic deletions (3 of 7 informative
cases, 43%). Allelic deletions on the following chromosomes were
detected at lower frequencies: chromosomes 2, 3, 7, 12, 13, 17, 22, and
XY. Tumors with allelic deletions on more than one chromosome had a
higher histological malignancy grade. Tumors from patients with advanced
disease all showed allelic deletions.
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