A BRCA1 Splice Site Variant Responsible for Familial Ovarian Cancer in a Han-Chinese Family

Objective Ovarian cancer(OC)is one of the most common and most lethal gynecological malignancies.OC has an age-dependent incidence and occurs more commonly in females older than 50 years old.Most OC patients are diagnosed at an advanced stage and have a poor prognosis.Germline mutations in the BRCA1 DNA repair associated gene(BRCA1)and the BRCA2 DNA repair associated gene(BRCA2)account for 20%–25%of epithelial ovarian cancer(EOC).BRCA1 germline mutations are more common in Chinese EOC patients.Methods This study reported a three-generation Han-Chinese family containing four EOC patients and a rectal adenocarcinoma patient.Whole-exome sequencing was performed on two EOC patients and an unaffected individual.Variant validation was also performed in all available members by Sanger sequencing.Results A heterozygous splice site variant,c.4358-2A>G in the BRCA1 gene,was identified.Bioinformatic analysis showed that the variant may change the splicing machinery.Conclusion The BRCA1 splice site variant,c.4358-2A>G was identified as the likely genetic cause for EOC,and may also be associated with the increased risk of rectal adenocarcinoma in the family.The findings were beneficial for genetic counseling,helpful for cancer prevention in other family members,and may facilitate therapy decision-making in the future to reduce cancer lethality.

Human genetic basis of coronavirus disease 2019

Coronavirus disease 2019(COVID-19)caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has resulted in considerable morbidity and mortality worldwide.COVID-19 incidence,severity,and mortality rates differ greatly between populations,genders,ABO blood groups,human leukocyte antigen(HLA)genotypes,ethnic groups,and geographic backgrounds.This highly heterogeneous SARS-CoV-2 infection is multifactorial.Host genetic factors such as variants in the angiotensin-converting enzyme gene(ACE),the angiotensin-converting enzyme 2 gene(ACE2),the transmembrane protease serine 2 gene(TMPRSS2),along with HLA genotype,and ABO blood group help to explain individual susceptibility,severity,and outcomes of COVID-19.This review is focused on COVID-19 clinical and viral characteristics,pathogenesis,and genetic findings,with particular attention on genetic diversity and variants.The human genetic basis could provide scientific bases for disease prediction and targeted therapy to address the COVID-19 scourge.

Overview and countermeasures of cancer burden in China

Cancer is one of the leading causes of human death worldwide.Treatment of cancer exhausts significant medical resources,and the morbidity and mortality caused by cancer is a huge social burden.Cancer has therefore become a serious economic and social problem shared globally.As an increasingly prevalent disease in China,cancer is a huge challenge for the country’s healthcare system.Based on recent data published in the Journal of the National Cancer Center on cancer incidence and mortality in China in 2016,we analyzed the current trends in cancer incidence and changes in cancer mortality and survival rate in China.And also,we examined several key risk factors for cancer pathogenesis and discussed potential countermeasures for cancer prevention and treatment in China.

Nasopharyngeal carcinoma:Advances in genomics and molecular genetics

Nasopharyngeal carcinoma （NPC） is a squamous-cell carcinoma that arises in the epithelial lining of the nasopharynx [1]. This neoplasm has a notable ethnic and geographic distribution, being of high prevalence in southern China but rare in other parts of the world [2]. Familial clustering of NPC has been observed in diverse populations [3]. Elevated levels of circulating free Epstein-Barr virus （EBV） DNA and EBV-related antibodies in sera, as well as EBV DNA in tumor ceils, have been consistently detected in individuals with NPC [4,5].

Long non-coding RNAs in cancer

Long non-coding RNAs （lncRNAs） are a group of RNA transcripts that exceed 200 nt in length, yet lack significant open reading frames （ORFs） [1-4]. In contrast to small non-coding RNAs （ncRNAs）, such as microRNAs （miR- NAs） [4-23], small interfering RNAs （siRNAs） [24-31] and transfer RNAs （tRNAs） [32-34], there are thousands of IncRNA genes discovered during the past three years in the human genome and most of their functions remain elusive. The long nucleotide chain of lncRNAs can either form a complex spatial structure and interact with protein factors, or provide a large segment for the concurrent binding of many molecules that collectively participate in genomic imprinting, X-chromosome silencing, chromosome modifi- cation, intranuclear transport, transcriptional activation and interference, thereby regulating cell growth, differentiation, development, senescence and death [35].

Trend analysis of cancer incidence and mortality in China

The National Central Cancer Registry of China （NCCRC） up- dated their nationwide statistics of cancer incidence and mor- tality in China according to 2013 population-based cancer registration data （due to the time required for data collection, quality control and analysis, the latest cancer statistics avail- able in China have a 3-year lag behind the current year）.

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Epstein-Barr virus(EBV)is associated with nasopharyngeal carcinoma(NPC)tumorigenesis.However,the mechanism(s)connecting EBV infection and NPC remain unclear.Recently,a new class of EBV microRNAs(miRNAs)has been described.To determine how EBV miRNAs control the expression of host genes,and to understand their potential role in NPC tumorigenesis,we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues.We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC.Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC.A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated,suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis.An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.

Circular RNA circCCNB1 inhibits the migration and invasion of nasopharyngeal carcinoma through binding and stabilizing TJP1 mRNA

Nasopharyngeal carcinoma(NPC)is a malignant tumor that usually occurs in people from Southeast Asia and Southern China.NPC is prone to migration and invasion,leading to poor prognosis.A large number of circular RNAs(circ RNAs)exacerbate the process of metastasis in NPC;however,their underlying mechanisms remain unclear.We found that the circular RNA circ CCNB1,encoded by the oncogene CCNB1,was downregulated in NPC biopsies and cell lines.In vitro assays show that circ CCNB1 inhibits NPC cell migration and invasion.Moreover,circ CCNB1 induces a protein,nuclear factor 90(NF90),to bind and prolong the half-life of tight junction protein 1(TJP1)m RNA.Upregulation of TJP1 enhances tight junctions between cancer cells and inhibits NPC cell migration and invasion.This study reveals a novel biological function of circ CCNB1 in the migration and invasion of NPC by enhancing the tight junctions of cancer cells by binding to NF90 proteins and TJP1 m RNA,and may provide a potential therapeutic target for NPC.