Endogenous immunoprecipitation was used to investigate protein interactions of SETD1A complex subunits. An unexpected interaction with the DNA damage protein RAD18 was confirmed for SETD1A but not for other subunits. SETD1A and RAD18 evoked a DNA damage repair phenotype and influenced each other's mRNA and protein expression.

Intraflagellar transport (IFT) is essential for the formation and function of the microtubule-based primary cilium, which acts as a sensory and signalling device at the cell surface. Consisting of IFT-A/B and BBSome cargo adaptors that associate with molecular motors, IFT transports protein into (anterograde IFT) and out of (retrograde IFT) the cilium. In this study, we identify the mostly uncharacterised ERICH3 protein as a component of the mammalian primary cilium. Loss of ERICH3 causes abnormally short cilia and results in the accumulation of IFT-A/B proteins at the ciliary tip, together with reduced ciliary levels of retrograde transport regulators, ARL13B, INPP5E and BBS5. We also show that ERICH3 ciliary localisations require ARL13B and BBSome components. Finally, ERICH3 loss causes positive (Smoothened) and negative (GPR161) regulators of sonic hedgehog signaling (Shh) to accumulate at abnormally high levels in the cilia of pathway-stimulated cells. Together, these findings identify ERICH3 as a novel component of the primary cilium that regulates cilium length and the ciliary levels of Shh signaling molecules. We propose that ERICH3 functions within retrograde IFT-associated pathways to remove signaling proteins from cilia.

The MCPH1 gene, also known as BRCT-repeat inhibitor of hTERT expression (BRIT1), has three BRCA1 carboxyl-terminal domains which is an important regulator of DNA repair, cell cycle checkpoints and chromosome condensation. MCPH1/BRIT1 is also known as a tumour suppressor in different types of human cancer. The expression level of the MCPH1/BRIT1 gene is decreased at the DNA, RNA or protein level in a number of types of cancers including breast cancer, lung cancer, cervical cancer, prostate cancer and ovarian cancer compared to normal tissue. This review also showed that deregulation of MCPH1/BRIT1 is significantly associated with reduced overall survival in 57% (12/21) and relapsed free survival in 33% (7/21) of cancer types especially in oesophageal squamous cell carcinoma and renal clear cell carcinoma. A common finding of this study is that the loss of MCPH1/BRIT1 gene expression plays a key role in promoting genome instability and mutations supporting its function as a tumour suppressor gene.

Background: In Saudi Arabia and across the world, the incidence of early-onset colorectal cancer (< 50 years) has increased. The diagnosis of EOCRC, on the other hand, is frequently delayed. It is critical to implement a national screening program to identify those group of patients who might benefit from early diagnosis. Method: A retrospective search was conducted using data from the Ministry of National Guard Health Affairs’ (MNG-HA) Cancer Registry. The population of 1440 CRC patients were eligible for the analyses. Patients’ demographics including age at diagnosis, gender, and marital status, were all reported. The demographic and clinical characteristics were assessed across early-onset and late-onset groups using Chi-square and Fisher exact test where appropriate. Results: CRC patients, early-onset CRC (18-50 years) was reported in 23.26%, mainly with advance disease. Late-onset (>50 years) CRC individuals have worse survival rate and higher probability of dying compared to early-onset CRC individuals. After age at diagnosis classification into three categories (18-40 years), (41-50 years), and (>50 years) the Kaplan-Meier Survival curve show that early-onset (18-40 years) CRC individuals had significantly better survival than (41-50 years), and (>50 years) CRC patients. Conclusions: Comparing our data to another screened population using US SEER datasets, we discovered a substantial difference in survival rates, with the SEER population having a considerably greater chance of survival. There is very little research on the significance of screening for Saudi CRC patients, and this is an issue that needs to be looked into more. Limitations: A study’s drawback is the lack of data for a variety of risk variables linked to colorectal cancer incidence, such as the KRAS mutation and environmental risk factors including BMI and smoking. More research with a nationally representative sample and comprehensive demographic and clinical data accessible is needed.

Objectives: This study aimed to investigate the prevalence and current treatment status of immune thrombocytopenia (ITP) in Taiwan.Methods: This was a retrospective study conducted using claim data collected from the Bureau of National Health Insurance (BNHI) of Taiwan from 2003 to 2007. ITP patients were identified using the ICD-9 code, 287.3 (primary thrombocytopenia), with two diagnoses separated by at least 14 days for diagnostic specificity. In addition, sensitivity analysis was based on 28 (ITP-28) and 84 (ITP-84) days.Results: ITP prevalence ranged from 10.35 to 11.02 (per 100,000 individuals) with an annual number of 2,300 to 2,500 patients, and sensitivity analyses using ITP-28 and ITP-84 criteria showed that the prevalence were "9.52 to 10.35" and "6.87 to 8.14" in 5,445 ITP patients, respectively. The median age of ITP-14 patients was 46.5 years. In children, the female-to-male ratio was nearly equal (0.93), whereas in adults, it was 1.91. About 3.9% received splenectomy, of which 64.3% were responsive to splenectomy. Further, 92.6% were responsive to steroids. The average costs per visit were US$ 36 and US$ 1,700 for outpatients and inpatients, respectively. For steroid-responsive patients, the mean costs for clinic visits and hospitalization were US$ 35 and US$ 1,415, respectively. In contrast, the medical expense for steroid-refractory patients was approximately one and a half times the costs for responsive patients (inpatient: US$ 54; outpatient: US$ 2,349). For splenectomy-responsive inpatients, the average expenses prior to, at, and after splenectomy were US$ 1,877, 5,476, and 2,061, respectively. For splenectomy-refractory inpatients, the costs were comparable to those of responsive patients (P> 0.05). On the contrary, there were significant differences between the expenditure for splenectomy-responsive and -refractory outpatients. Among ITP patients in Taiwan, 7.4% and 6.4% had hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, respectively, and 1.5% had both HBV and HCV infections. Patients with HBV were significantly high in the splenectomy group (splenectomy vs. non-splenectomy 11.7% vs. 7.2%, P = 0.01), and those who were more responsive to splenectomy had a low HCV infection rate, i.e., 14.5% had HCV infection in splenectomy-refractory group vs. 4.38% in splenectomy-responsive group (P = 0.02). Conclusions:The epidemiology of ITP in Taiwan, including the age and sex, was comparable with that in western countries, except with lower incidence of splenectomy in our patients. The status of HBV and HCV infection in splenectomized patients should be closely monitored. The medical expenditure in Taiwan was much lower than that in western countries. We suggest that novel agents or more aggressive treatment strategies should be further explored or considered in Taiwan.