Dynamic structure of the <i>SPANX</i> gene cluster mapped to the prostate cancer susceptibility locus <i>HPCX</i> at Xq27

Kouprina, Natalay; Pavlı́ček, Adam; Noskov, Vladimir N.; Solomon, Greg; Otstot, John; Isaacs, William; Carpten, John D.; Trent, Jeffrey M.; Schleutker, Johanna; Barrett, J. Carl; Jurka, Jerzy; Larionov, Vladimir

doi:10.1101/gr.4212705

Cited by 38 publications

(63 citation statements)

References 54 publications

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“…25,34 So far, the function of SPANXB or the other SPANX genes has not been studied in detail, but all five SPANX genes are present on the 750 kb Xq region linked to prostate cancer susceptibility, and deregulation of either one has been suggested as a possible mechanism for malignant transformation of prostate cells. 35 This is supported by experimental models showing that ectopic expression of SPANXC induces transformation in mammalian cells. 35 The association between SPANXB expression and presence of ETV6/RUNX1 may also be of importance for future treatment modalities, as SPANXB, normally present only in the immune-privileged testis, has been suggested to be an ideal target for tumor immunotherapy.…”

Section: Discussionsupporting

confidence: 59%

“…35 This is supported by experimental models showing that ectopic expression of SPANXC induces transformation in mammalian cells. 35 The association between SPANXB expression and presence of ETV6/RUNX1 may also be of importance for future treatment modalities, as SPANXB, normally present only in the immune-privileged testis, has been suggested to be an ideal target for tumor immunotherapy. 34 18 smoothed z-scores (25-probe sliding mean) were plotted for all cases.…”

Section: Discussionsupporting

confidence: 59%

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Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region

et al. 2007

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Seventeen ETV6/RUNX1-positive pediatric acute lymphoblastic leukemias were investigated by high-resolution array-based comparative genomic hybridization (array CGH), gene expression profiling and fluorescence in situ hybridization. Comparing the array CGH and gene expression patterns revealed that genomic imbalances conferred a great impact on the expression of genes in the affected regions. The array CGH analyses identified a high frequency of cytogenetically cryptic genetic changes, for example, del(9p) and del(12p). Interestingly, a duplication of Xq material, varying between 30 and 60 Mb in size, was found in 6 of 11 males (55%), but not in females. Genes on Xq were found to have a high expression level in cases with dup(Xq); a similar overexpression was confirmed in t(12;21)-positive cases in an external gene expression data set. By studying the expression profile and the proposed function of genes in the minimally gained region, several candidate target genes (SPANXB, HMGB3, FAM50A, HTATSF1 and RAP2C) were identified. Among them, the testis-specific SPANXB gene was the only one showing a high and uniform overexpression, irrespective of gender and presence of Xq duplication, suggesting that this gene plays an important pathogenetic role in t(12;21)-positive leukemia.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionsupporting

confidence: 59%

Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region

et al. 2007

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“…Originally, the SPANX family of genes was proposed as putative candidates for the HPCX-susceptibility locus. 43 However, recent studies have not identified mutations in any of these genes that definitely account for PrCa risk in X-linked HPC families. 44 Also found by conditioning on linkage to chromosome 2 was a significant peak on 12q21-q23, with an OSA LOD of 3.67 in families unlinked to chromosome 2.…”

Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

et al. 2012

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Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (DLOD ¼ 3.193, empirical P ¼ 0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD ¼ 2.541, DLOD ¼ 1.651, P ¼ 0.03) and 22q11.1-q11.21 (OSA LOD ¼ 2.395, DLOD ¼ 2.36, P ¼ 0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families.

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“…These data were confirmed by an increased expression of the protein LDOC-1 in the tissues of PCa patients compared with normal prostate tissues. Gene conversions on the X chromosome (LDOC-1 maps in Xq27) have been linked with genetic diseases and disorders (21). These variations lead to haplotypes with an increased susceptibility to PCa; therefore it cannot be excluded that any rearrangements may favor an overexpression of LDOC-1 in PCa.…”

Section: Discussionmentioning

confidence: 99%

Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer

et al. 2016

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Abstract. Numerous genetic alterations have been implicated in the development of prostate cancer (PCa). DNA and protein microarrays have enabled the identification of genes associated with apoptosis, which is important in PCa development. Despite the molecular mechanisms are not entirely understood, inhibition of apoptosis is a critical pathophysiological factor that contributes to the onset and progression of PCa. Leucine zipper, down-regulated in cancer 1 (LDOC-1) is a known regulator of the nuclear factor (NF)-mediated pathway of apoptosis through the inhibition of NF-κB. The present study investigated the expression of the LDOC-1 gene in LNCaP, PC-3, PNT1A and PNT2 prostate cell lines by reverse transcription-quantitative polymerase chain reaction. In addition LDOC-1 protein expression in normal prostate tissues and PCa was studied by immunohistochemistry. LDOC-1 messenger RNA resulted overexpressed in LNCaP and PC-3 PCa cell lines compared with the two normal prostate cell lines PNT1A and PNT2. The results of immunohistochemistry demonstrated a positive cytoplasmic LDOC-1 staining in all PCa and normal prostate samples, whereas no nuclear staining was observed in any sample. Furthermore, a more intense signal was evidenced in PCa samples. LDOC-1 gene overexpression in PCa suggests an activity of LDOC-1 in PCa cell lines.

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Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27

Cited by 38 publications

References 54 publications

Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region

Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

Leucine zipper, down regulated in cancer-1 gene expression in prostate cancer

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