Genetic changes in stage pT2N0 prostate cancer studied by comparative genomic hybridization

Wolter, H.; Gottfried, H. W.; Mattfeldt, Torsten

doi:10.1046/j.1464-4096.2001.01722.x

Cited by 30 publications

(19 citation statements)

References 30 publications

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“…Our rather low results for 8q gains in early stage tumors are supported by some comparative genomic hybridization analyses with comparable frequencies between 6% and 9% (32,(38)(39)(40). From the data, it seems that these studies had preferably included early stage tumors.…”

Section: 6%supporting

confidence: 73%

“…Our notion that the frequencies of 8p deletions and 8q gains found in this project may reflect the true fraction of cancers having a "dominant" proportion of such cells is supported by comparable numbers found by methods analyzing "average copy numbers" of genomic material, such as loss of heterozygosity or comparative genomic hybridization. Studies analyzing comparable tumor populations by comparative genomic hybridization have reported between 17.6% and 32% 8p deletions for primary tumors (32,(38)(39)(40), and between 48% and 73% for advanced tumors (41)(42)(43)(44). In a recent meta-analysis, chromosome 8p was the most deleted region in the genome (45).…”

Section: 6%mentioning

confidence: 99%

See 1 more Smart Citation

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

Gammal¹,

Brüchmann²,

Zustin³

et al. 2010

Clinical Cancer Research

123

107

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Purpose: Deletions of 8p and gains of 8q belong to the most frequent cytogenetic alterations in prostate cancer. The target genes of these alterations and their biological significance are unknown.Experimental Design: To determine the relationship between chromosome 8 changes, and prostate cancer phenotype and prognosis, a set of 1.954 fully annotated prostate cancers were analyzed in a tissue microarray format by fluorescence in situ hybridization.Results: Both 8p deletions and 8q gains increased in number during different stages of prostate cancer progression. 8p deletions/8q gains were found in 26.1%/4.8% of 1,239 pT 2 cancers, 38.5%/9.8% of 379 pT 3a cancers, 43.5%/8.9% of 237 pT 3b cancers, 40.7%/14.8% of 27 pT 4 cancers, 39.1%/34.8% of 23 nodal metastases, 51.9%/33.3% of 27 bone metastases, and 45.5%/59.9% of 22 hormone refractory cancers (P < 0.0001 each). Both 8p deletions and 8q gains were also significantly associated with high Gleason grade and with each other (P < 0.0001 each). In primary tumors, 8p deletions were seen in only 27.3% of 1,882 cancers without 8q gain but in 57.4% of 122 tumors with 8q gain (P < 0.0001). Among cancers treated with radical prostatectomy, 8p deletions (P = 0.003) and 8q gains (P = 0.02) were associated with biochemical tumor recurrence. However, multivariate analysis (including prostate-specific antigen, pT/pN stage, Gleason score, and surgical margin status) did not reveal any statistically independent effect of 8p or 8q alterations on biochemical tumor recurrence.Conclusions: 8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application. Clin Cancer Res; 16(1); 56-64. ©2010 AACR.Prostate cancer is the most frequently diagnosed malignancy and the second most frequent cause of cancerrelated death among western males (1).Currently, clinical prediction tools rely solely on clinical (clinical stage), serologic (prostate-specific antigen), and histologic variables (Gleason grading; ref. 2).Because the development and progression of cancer is driven by molecular alterations, the analysis of molecular features may eventually allow better prediction of the behavior of individual cancers.Alterations on the DNA level would be especially suitable as prognostic markers. DNA alterations have the advantage of being less vulnerable to perioperative and postoperative ischemia or fixation procedures than RNA or proteins (3, 4). Deletions of 8p and gains of 8q are among the most frequent genomic alterations in prostate cancer. Several studies have proposed a relationship between 8p−/8q+ with adverse histopathologic findings (5-11). Studies suggesting associations with prostatespecific antigen progression, however, were limited to <100 cancers (12)(13)(14). Whereas considerable evidence points toward a role of chromosome 8 changes in prostate cancer biology, it is also evident that much larger patient cohorts are now needed to further cl...

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Section: 6%supporting

confidence: 73%

Section: 6%mentioning

confidence: 99%

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

Gammal¹,

Brüchmann²,

Zustin³

et al. 2010

Clinical Cancer Research

123

107

View full text Add to dashboard Cite

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“…This is particularly important since the STAT5A/B genes are located on chromosome 17 (Clark et al 2003) that is frequently altered in both incidental and hereditary prostate cancers (Gillanders et al 2004). Chromosome 17q showed allelic imbalance in prostate cancer (Latil et al 1994, Bova & Isaacs 1996, Alers et al 2000, Kasahara et al 2002, Wolter et al 2002a,b, Verhage et al 2003, von Knobloch et al 2004, and gains in chromosome 17q were detected in five studies (Bova & Isaacs 1996, Alers et al 2000, Kasahara et al 2002, Wolter et al 2002a. Moreover, three large studies linked a prostate cancer susceptibility gene to chromosome 17q (17q22) (Lange et al 2003, Gillanders et al 2004, Zuhlke et al 2004, suggesting involvement of genes in this region in an inherited form of prostate cancer.…”

Section: Pathways Leading To Constitutive Activation Of Stat5a/b In Pmentioning

confidence: 99%

Signal transducer and activator of transcription 5A/B in prostate and breast cancers

Tan

Nevalainen

2008

Endocrine Related Cancer

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Protein kinase signaling pathways, such as Janus kinase 2-Signal transducer and activator of transcription 5A/B (JAK2-STAT5A/B), are of significant interest in the search for new therapeutic strategies in both breast and prostate cancers. In prostate cancer, the components of the JAK2-STAT5A/B signaling pathway provide molecular targets for small-molecule inhibition of survival and growth signals of the cells. At the same time, new evidence suggests that the STAT5A/B signaling pathway is involved in the transition of organ-confined prostate cancer to hormonerefractory disease. This implies that the active JAK2-STAT5A/B signaling pathway potentially provides the means for pharmacological intervention of clinical prostate cancer progression. In addition, active STAT5A/B may serve as a prognostic marker for identification of those primary prostate cancers that are likely to progress to aggressive disease. In breast cancer, the role of STAT5A/B is more complex. STAT5A/B may have a dual role in the regulation of malignant mammary epithelium. Data accumulated from mouse models of breast cancer suggest that in early stages of breast cancer STAT5A/B may promote malignant transformation and enhance growth of the tumor. This is in contrast to established breast cancer, where STAT5A/B may mediate the critical cues for maintaining the differentiation of mammary epithelium. In addition, present data suggest that activation of STAT5A/B in breast cancer predicts favorable clinical outcome. The dual nature of STAT5A/B action in breast cancer makes the therapeutic use of STAT5 A/B more complex.

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“…The hMystique gene is located on chromosome 8p21.2. Allelic loss of chromosome 8p21 occurs frequently in advanced ovarian and prostate cancers (Brown et al, 1999;Swalwell et al, 2002;Wolter et al, 2002). Other PDZ-LIM domain proteins have been associated with tumor suppressor function.…”

Section: Igf-i-responsive Pdz-lim Protein In Epithelial Cellsmentioning

confidence: 99%

Mystique Is a New Insulin-like Growth Factor-I-regulated PDZ-LIM Domain Protein That Promotes Cell Attachment and Migration and Suppresses Anchorage-independent Growth

Loughran

Healy

Kiely

et al. 2005

MBoC

116

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By comparing differential gene expression in the insulin-like growth factor (IGF)-IR null cell fibroblast cell line (R؊ cells) with cells overexpressing the IGF-IR (R؉ cells), we identified the INTRODUCTIONInsulin-like growth factor (IGF)-I and IGF-II are ligands for the widely expressed IGF-I receptor tyrosine kinase, which promotes mitogenesis and cell survival (reviewed in Adams et al., 2000). The IGF-IR is essential for normal growth during embryonic development and promotes cell survival and migration. Circulating IGFs and the IGF-IR signaling pathways also have been associated with cancer progression (reviewed in LeRoith and Roberts, 2003). In a mouse model of pancreatic islet cell tumorigenesis, endogenous IGF-IR expression was up-regulated at invasive regions of the tumors, and ectopic IGF-IR expression resulted in the accelerated development of highly invasive and metastatic carcinomas (Lopez and Hanahan, 2002). Conversely, the suppression of IGF-IR expression by antisense strategies (Resnicoff, 1998) or blocking antibodies results in decreased tumor growth and decreased metastatic capacity in tumor cell models (Maloney et al., 2003). Signals from the IGF-IR associated with survival, tumorigenicity, and metastasis are associated with the C terminus of the receptor (O'Connor et al., 1997;Brodt et al., 2001;Baserga et al., 2003).Cell migration and invasion are complex processes that require the coordination of signals from both adhesion and growth factor receptors. Signals from the IGF-IR can interact with those from integrins to initiate the formation of signaling complexes necessary for the formation and disassembly of cell adhesions with the extracellular matrix (ECM) (Doerr and Jones, 1996;Brooks et al., 1997). These signals involve enhancement of Shc phosphorylation (Mauro et al., 1999;Jackson et al., 2000;Kim et al., 2004), regulation of focal adhesion kinase phosphorylation at focal adhesions (Manes et al., 1999), differential regulation of signals by scaffolding proteins such as RACK1 (Hermanto et al., 2002;Kiely et al., 2002), signals from reorganization of the cytoskeleton (Casamassima and Rozengurt, 1998;Kim and Feldman, 1998;Guvakova et al., 2002), expression of angiogenic and invasive factors , regulation of cadherin location (Playford et al., 2000;Pennisi et al., 2002), and transactivation of the epidermal growth factor (EGF) receptor (Burgaud and Baserga, 1996;Roudabush et al., 2000). How all of these events are coordinated during cell migration or invasion, or how some of these signals are enhanced in metastatic cancer, is still poorly understood.IGF-I induces expression of several genes that promote cell migration and cancer progression, including ␤-catenin (Playford et al., 2000), the cadherin complex protein ZO-1 (Mauro et al., 2001), the angiogenic factor vascular endothelial growth factor (Miele et al., 2000), the metalloprotease MT1 MMP , and heparin-binding EGF-like growth factor (Mulligan et al., 2002 refractory to cellular transformation by several oncogenes (Sell et al., 1994), ...

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Genetic changes in stage pT2N0 prostate cancer studied by comparative genomic hybridization

Cited by 30 publications

References 30 publications

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

Chromosome 8p Deletions and 8q Gains are Associated with Tumor Progression and Poor Prognosis in Prostate Cancer

Signal transducer and activator of transcription 5A/B in prostate and breast cancers

Mystique Is a New Insulin-like Growth Factor-I-regulated PDZ-LIM Domain Protein That Promotes Cell Attachment and Migration and Suppresses Anchorage-independent Growth

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