Tumor Protein p53 and K-ras Gene Mutations in Peruvian Patients with Gallbladder Cancer

Background: Recent studies have shown that genetic alterations are associated with the effect of patient geographiclocation on gallbladder cancer development. Peru has a high incidence of gallbladder cancer, but causative factorshave not yet been identified. We examined the frequency of mutations in TP53 and K-ras genes in Peruvian patientswith gallbladder cancer, and compared this with data from Bolivia, Hungary, Chile, and Japan, which have a highgallbladder cancer incidence. Methods: DNA was extracted from formalin-fixed paraffin-embedded gallbladder tissuesections of 30 gallbladder cancer patients (9 men and 21 women) obtained using microdissection. Mutations in exons5 to 8 of TP53 and codons 12, 13, and 61 of K-ras were examined using direct sequencing. Results: TP53 mutationswere observed in 10 (33.3%) of patients, but K-ras mutations were absent. Nine (90%) TP53 mutations were pointmutations (7 missense and 2 silent mutations), and the most frequent substitution was a G:C to A:T transition. G:C toA:T transitions at the CpG site or G:C to T:A transversions were found in one patient each. No significant differenceswere found in the frequency of TP53 and K-ras mutations among patients in the 5 countries. Conclusions: Our findingssuggest that endogenous mechanisms and exogenous carcinogens may affect the carcinogenic process in Peruviangallbladder cancer patients, similar to that in Bolivian patients. Further studies with a larger sample size are neededto clarify these findings.     

Differential Expression of PD-L1 Between Sporadic and VHL-Associated Hereditary Clear-Cell Renal Cell Carcinoma and Its Correlation With Clinicopathological Features

Background

Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.

Will Mutations in the Spike Protein of SARS-CoV-2 Lead to the Failure of COVID-19 Vaccines?

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has spread worldwide since it was first identified in Wuhan, China, at the end of 2019. With the global transmission of the virus, a large number of SARS-CoV-2 variants have also appeared, especially, emerging strains that have recently been discovered in the United Kingdom (variant 20I/501Y.V1, lineage B.1.1.7), South Africa (variant 20H/501Y.V2, lineage B.1.351), and Brazil (variant 20 J/501Y.V3, and lineage P.1). The common feature of these variants is that they share the N501Y mutation involving the SARS-CoV-2 spike (S) protein, which is precisely the target of most COVID-19 vaccines. Furthermore, mutations such as N501Y, E484K, and K417N in the S protein may affect viral fitness and transmissibility. However, current research on the impact of these variants on COVID-19 vaccines is still lacking. Herein, we briefly explain why most COVID-19 vaccines target the S protein, update the progress of research regarding S protein-related COVID-19 vaccines, review the latest studies concerning the effects of S protein variants on COVID-19 vaccines, and finally, propose certain strategies to deal with SARS-CoV-2 variants.     

葡萄糖激酶W257R突变致青少年发病的成人型糖尿病一家系分析

青少年发病的成人型糖尿病（MODY）是一类以常染色体显性模式遗传的单基因疾病，临床表现以无症状、轻度空腹血糖升高为特征，很少出现糖尿病并发症。本文报道一例中国人群中葡萄糖激酶（GCK）基因新发W257R突变所致的MODY。在先证者及父亲、弟弟中均发现GCK基因（Chr744187343）第7号外显子的杂合突变c.769T>C（p.W257R）。该家系中W257R突变在中国人群中为首发。     

靶向测序诊断黑棘皮病1家系

【摘要】 报道临床症状不典型的家族性黑棘皮病1家系。先证者女，4岁，自1周岁时，颈部、腹部出现黑色斑片，近年来逐渐扩大至唇周、躯干前部。腹部皮肤全反式共聚焦显微镜检查可见乳头环下延扭曲及沟壑结构，乳头环内可见中高折光颗粒结构。先证者父亲及祖母既往有类似病史，但随着年龄增长色素沉着自发性消退，仅有局部皮纹增粗。采集先证者及父母、祖母外周血，对先证者外周血DNA行Panel靶向测序，结果显示，先证者存在FGFR3基因14号外显子c.1949A>C（p.Lys650Thr）错义突变，Sanger测序验证证实先证者及其父亲和祖母均存在此突变。诊断：家族性黑棘皮病。     

Mutational Analysis of the Rhodopsin Gene in Sector Retinitis Pigmentosa

Background: To determine the role of rhodopsin (RHO) gene mutations in patients with sector retinitis pigmentosa (RP) from Northern Ireland.

Design: A case series of sector RP in a tertiary ocular genetics clinic.

Participants: Four patients with sector RP were recruited from the Royal Victoria Hospital (Belfast, Northern Ireland) and Altnagelvin Hospital (Londonderry, Northern Ireland) following informed consent.

Methods: The diagnosis of sector RP was based on clinical examination, International Society for Clinical Electrophysiology of Vision (ISCEV) standard electrophysiology, and visual field analysis. DNA was extracted from peripheral blood leucocytes and the coding regions and adjacent flanking intronic sequences of the RHO gene were polymerase chain reaction (PCR) amplified and cycle sequenced.

Main Outcome Measure: Rhodopsin mutational status.

Results: A heterozygous missense mutation in RHO (c.173C?>?T) resulting in a non-conservative substitution of threonine to methionine (p. Thr58Met) was identified in one patient and was absent from 360 control individuals. This non-conservative substitution (p.Thr58Met) replaces a highly evolutionary conserved polar hydrophilic threonine residue with a non-polar hydrophobic methionine residue at position 58 near the cytoplasmic border of helix A of RHO.

Conclusions: The study identified a RHO gene mutation (p.Thr58Met) not previously reported in RP in a patient with sector RP. These findings outline the phenotypic variability associated with RHO mutations. It has been proposed that the regional effects of RHO mutations are likely to result from interplay between mutant alleles and other genetic, epigenetic and environmental factors.     

Impact of 3′UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population

ObjectiveSeveral studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3′ untranslated region (3′UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3′UTR regions of the KRAS gene and the effect of KRAS 3′UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT.MethodsCodons 12, 13, and 61 and 3′UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients.ResultsWe defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3′UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.