In this study, we characterize the molecular and functional features of a novel protein called SPOC1. SPOC1 RNA expression was previously reported to be highest in highly proliferating tissues and increased in a subset of ovarian carcinoma patients, which statistically correlated with poor prognosis and residual disease. These observations implied that SPOC1 might play a role in cellular proliferation and oncogenesis. Here we show that the endogenous SPOC1 protein is labile, primarily chromatin associated and its expression as well as localization are regulated throughout the cell cycle. SPOC1 is dynamically regulated during mitosis with increased expression levels and biphasic localization to mitotic chromosomes indicating a functional role of SPOC1 in mitotic processes. Consistent with this postulate, SPOC1 siRNA knockdown experiments resulted in defects in mitotic chromosome condensation, alignment and aberrant sister chromatid segregation. Finally, we have been able to show, using micrococcal nuclease (MNase) chromatin-digestion assays that SPOC1 expression levels proportionally influence the degree of chromatin compaction. Collectively, our findings show that SPOC1 modulates chromatin structure and that tight regulation of its expression levels and subcellular localization during mitosis are crucial for proper chromosome condensation and cell division.

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We report the identification of a novel human gene (SPOC1) which encodes a protein with a PHD-finger domain. The gene is located in chromosomal region 1p36.23, a region implicated in tumor development and progression. RNA in situ hybridization experiments showed strong SPOC1 expression in some rapidly proliferating cell types, such as spermatogonia, but not in nonproliferating mature spermatocytes. In addition, high SPOC1 mRNA expression was observed in several ovarian cancer cell lines. This prompted us to systematically examine SPOC1 expression in ovarian cancer in relation to prognosis. SPOC1 mRNA expression was quantified in tumor tissue of 103 patients with epithelial ovarian cancer. Interestingly, SPOC1 was associated with residual disease, whereby patients with unresectable tumors showed higher levels compared to patients without residual tumor tissue after surgery ( p = 0.029). The univariable proportional hazards model showed an association between SPOC1 expression and survival ( p = 0.043, relative risk = 1.535). Median survival time was 1,596 days for patients with low SPOC1 expression vs. only 347 days for patients with high expression, using Kaplan-Meier analysis. However, SPOC1 was not associated with survival when multivariable analysis was adjusted for residual disease. This can be explained by the correlation between residual disease and SPOC1 expression. In conclusion, SPOC1 is a novel PHD-finger protein showing strong expression in spermatogonia and ovarian cancer cells. SPOC1 overexpression was associated with unresectable carcinomas and shorter survival in ovarian cancer. ' 2005 Wiley-Liss, Inc.

IntroductionLymphogranuloma venereum (LGV) is a sexually transmitted infection (STI) caused by chlamydia trachomatis (CT) genotype L (L1, L2 and L3). Recent outbreaks of LGV in Europe and North America affected mainly men who have sex with men (MSM). Infections with CT serotypes D-K are mostly associated with mild symptoms or may be clinically silent. However, infections with L genotypes are more invasive and induce anogenital ulcer or inguinal lymphadenopathy.Materials and MethodsBetween 2003 and 2013, anal or genital CT infections were diagnosed in 471 symptomatic patients attending the Infectious Diseases Center Hamburg (ICH). CT DNA was detected by PCR. CT genotyping of positive samples was performed by sequence analyses of omp1 PCR products (samples between 2003 and 2010). Samples between 2012 and 2013 were analyzed by genotype L specific real-time PCR.ResultsIn total, 221 LGV patients were identified (3 in 2003; 11 in 2004; 26 in 2005; 33 in 2006; 24 in 2007; 16 in 2008; 18 in 2009; 15 in 2010; 17 in 2011; 26 in 2012 and 32 in 2013). One hundred ninety-eight of 221 (89.6%) patients with LGV were HIV-infected; 10 of 221 (4.5%) were HIV-negative, and the HIV-status unknown in 13 (5.9%). The majority of LGV positive patients (204/221; 92%) had anorectal symptoms (bloody proctitis, rectal pain, purulent or mucous discharge, tenesmus, constipation), compared to 17/221 (8%) who presented with genital symptoms as urethritis, genital ulcer or inguinal lymphadenopathy. Of 283 CT-positive patients with anorectal symptoms, genotype L was detected in 205 (72%), while non-L genotypes (D-K) were found in 78 (28%). In contrast, genotype L was found in only 6% of patients with genital symptoms (11/177), whereas 94% (166/177) were infected with non-L genotypes only.ConclusionsThe epidemic of LGV among predominantly HIV+ MSM is ongoing. LGV might be underdiagnosed, especially in patients with anorectal symptoms. Infections with CT serotypes D-K are more often associated with urogenital symptoms or asymptomatic infection, whereas LGV genotypes are found most frequently in patients with rectal/intestinal symptoms. Anorectal CT infections in MSM should be further characterized by genotyping for LGV, as for LGV three weeks of doxycycline treatment are recommended. CT genotypes D-K generally require shorter antibiotic treatment. If CT genotyping is not available, the duration of treatment should be prolonged to three weeks empirically for CT-positive patients with anorectal or intestinal symptoms.