Disturbed Expression of Splicing Factors in Renal Cancer Affects Alternative Splicing of Apoptosis Regulators, Oncogenes, and Tumor Suppressors

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer. One of the processes disturbed in this cancer type is alternative splicing, although phenomena underlying these disturbances remain unknown. Alternative splicing consists of selective removal of introns and joining of residual exons of the primary transcript, to produce mRNA molecules of different sequence. Splicing aberrations may lead to tumoral transformation due to synthesis of impaired splice variants with oncogenic potential. In this paper we hypothesized that disturbed alternative splicing in ccRCC may result from improper expression of splicing factors, mediators of splicing reactions. METHODOLOGY/PRINCIPAL FINDINGS: Using real-time PCR and Western-blot analysis we analyzed expression of seven splicing factors belonging to SR proteins family (SF2/ASF, SC35, SRp20, SRp75, SRp40, SRp55 and 9G8), and one non-SR factor, hnRNP A1 (heterogeneous nuclear ribonucleoprotein A1) in 38 pairs of tumor-control ccRCC samples. Moreover, we analyzed splicing patterns of five genes involved in carcinogenesis and partially regulated by analyzed splicing factors: RON, CEACAM1, Rac1, Caspase-9, and GLI1. CONCLUSIONS/SIGNIFICANCE: We found that the mRNA expression of splicing factors was disturbed in tumors when compared to paired controls, similarly as levels of SF2/ASF and hnRNP A1 proteins. The correlation coefficients between expression levels of specific splicing factors were increased in tumor samples. Moreover, alternative splicing of five analyzed genes was also disturbed in ccRCC samples and splicing pattern of two of them, Caspase-9 and CEACAM1 correlated with expression of SF2/ASF in tumors. We conclude that disturbed expression of splicing factors in ccRCC may possibly lead to impaired alternative splicing of genes regulating tumor growth and this way contribute to the process of carcinogenesis

10Kin1day: A Bottom-Up Neuroimaging Initiative.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Niezwykły objaw raka jasnokomórkowego – opis przypadku

The metabolism of neoplastic cells is perceived as the cause of atherothrombotic incidents in cancers since the 19th century. Those incidents occur in 1–11% cancer cases. In clear cell carcinoma, accounting for 5% of ovarian cancers, atherothrombotic incidents tend to occur 2.5 times more frequently. Clear cell carcinoma is diagnosed earlier and at a younger age compared to other ovarian cancers. The cancer is also characterized by drug resistance to standard treatment. A 47-year-old patient was admitted to the Department of Gynaecology and Obstetrics of School of Medicine in Katowice to treat a tumor of the right ovary. The tumor was detected a month before during the diagnostics of an ischemic stroke which occurred despite no risk factors being present. A laparotomy was performed and the tumor, left adnexa and uterus were removed, according to ovarian cancer protocol. Histopathological examination confirmed the diagnosis of adenocarcinoma clarocellulare (clear cell carcinoma – CCC). The patient was referred for further oncological treatment on 5th day after surgery. Oncological alertness needs to be maintained in cases of unexplained atherothrombotic incidents. An interdisciplinary approach can improve patients’ prognosis by diagnosing the cancer earlier.Choroba nowotworowa już od dawna uznawana jest za przyczynę incydentów zakrzepowo-zatorowych. Incydenty te występują w 1–11% przypadków raków. W raku jasnokomórkowym, który stanowi około 5% nowotworów złośliwych jajnika, incydenty zakrzepowo-zatorowe występują 2,5 razy częściej niż w innych typach histologicznych. Rak jasnokomórkowy jest rozpoznawany u młodszych kobiet i we wcześniejszym stadium. Nowotwór cechuje też chemiooporność na standardowe leczenie. Kobieta 47-letnia została przyjęta do Kliniki Ginekologii i Położnictwa Wydziału Lekarskiego w Katowicach w celu leczenia guza (raka) przydatków prawych, którego wykryto miesiąc wcześniej w trakcie diagnostyki udaru niedokrwiennego. Udar wystąpił mimo braku czynników obciążających. Wykonano laparotomię według protokołu raka jajnika. Badanie histopatologiczne potwierdziło rozpoznanie: rak jasnokomórkowy (clear cell carcinoma – CCC). Pacjentkę w 5 dobie po operacji wypisano ze szpitala i skierowano do dalszego leczenia onkologicznego. Interdyscyplinarne podejście zespołu lekarskiego może poprawić rokowanie pacjentek przez wcześniejsze wykrycie nowotworu. Należy zachować czujność onkologiczną w przypadku niewyjaśnionego incydentu zakrzepowo-zatorowego

Diagnostic yield is dependent on monitoring duration. Insights from a full-disclosure mobile cardiac telemetry system

Background: Despite the advancement of electrocardiogram (ECG) monitoring methods, the most important factor influencing diagnostic yield (DY) may still be monitoring duration. Ambulatory ECG monitoring, typically with 24–48 hours duration, is widely used but may result in underdiagnosis of rare arrhythmias.Aims: This study aimed to examine the relationship between the DY and monitoring duration in a large patient cohort and investigate sex and age differences in the presentation of arrhythmias. Methods: The study population consisted of 25 151 patients (57.8% women; median [interquartile range, IQR], 71 [64–78] years), who were examined with mobile cardiac telemetry during 2017 in the United States, using the PocketECGTM that continuously transmits a signal on a beat-to-beat basis. We investigated the occurrence of atrial fibrillation at a burden of both ≤1% (atrial fibrillation [AF], ≤1%) and ≤10% (AF ≤10%), premature ventricular contractions (PVC; >10 000 per 24 hours), non-sustained ventricular tachycardias (nsVT), sustained ventricular tachycardias (VT ≥30 seconds), atrioventricular blocks (AVB), pauses of >3 seconds duration, and bradycardia  (heart rate <40 beats per minute for ≥60 seconds).Results: The median (IQR) recording duration was 15.4, 8.2–28.2) days. The DY increased gradually with monitoring duration for all types of investigated arrhythmias. Compared to DY after up to 30 days of monitoring, a standard 24 hours monitoring resulted in DY for males/females of 20%/18% for AF ≤1%, 29%/28% for AF ≤10%, 45%/40% for PVCs, 17%/11% for nsVT, 17%/11% for VT ≥30 seconds, 49%/42 for AVB, 27%/20% for pauses, 36%/29% for bradycardia. Conclusion: A substantial number of patients suffering from arrhythmias may remain undiagnosed due to insufficient ECG monitoring time