Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients

BACKGROUND Adaptor protein,phosphotyrosine interacting with PH domain and leucine zipper 1(APPL1)plays a crucial role in regulating insulin signaling and glucose metabolism.Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14(MODY14).Currently,only two mutations[c.1655T>A(p.Leu552*)and c.281G>A p.(Asp94Asn)]have been identified in association with this disease.Given the limited understanding of MODY14,it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations.AIM To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain.METHODS Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study.Whole exome sequencing was performed on the patients as well as their family members.The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis.In addition,the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments.Finally,the impact of these variants on APPL1 protein expression and the insulin pathway were assessed,and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored.RESULTS A total of five novel mutations were identified,including four missense mutations(Asp632Tyr,Arg633His,Arg532Gln,and Ile642Met)and one intronic mutation(1153-16A>T).Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions.The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster.In addition,multiple alignment of amino acid sequences showed that the Arg532Gln,Asp632Tyr,and Arg633His variants were conserved across different species.Moreover,in in vitro functional experiments,both the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels,indicating their pathogenic nature.Therefore,based on the patient’s clinical and family history,combined with the results from bioinformatics analysis and functional experiment,the c.1894G>T(at Asp632Tyr)and c.1595G>A(at Arg532Gln)mutations were classified as pathogenic mutations.Importantly,all these mutations were located within the phosphotyrosinebinding domain of APPL1,which plays a critical role in the insulin sensitization effect.CONCLUSION This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

Co-existing squamous cell carcinoma and chronic myelomonocytic leukemia with ASXL1 and EZH2 gene mutations:A case report

BACKGROUND Chronic myelomonocytic leukemia(CMML),a rare clonal hematopoietic stem cell disorder characterized by myelodysplastic syndrome and myeloproliferative neoplasms,has a generally poor prognosis,and easily progresses to acute myeloid leukemia.The simultaneous incidence of hematologic malignancies and solid tumors is extremely low,and CMML coinciding with lung malignancies is even rarer.Here,we report a case of CMML,with ASXL1 and EZH2 gene mutations,combined with non-small cell lung cancer(lung squamous cell carcinoma).CASE SUMMARY A 63-year-old male,suffering from toothache accompanied by coughing,sputum,and bloody sputum for three months,was given a blood test after experiencing continuous bleeding resulting from a tooth extraction at a local hospital.Based on morphological results,the patient was diagnosed with CMML and bronchoscopy was performed in situ to confirm the diagnosis of squamous cell carcinoma in the lower lobe of the lung.After receiving azacitidine,programmed cell death protein 1,and platinum-based chemotherapy drugs,the patient developed severe myelosuppression and eventually fatal leukocyte stasis and dyspnea.CONCLUSION During the treatment and observation of CMML and be vigilant of the growth of multiple primary malignant tumors.

Clinical manifestations of adult hereditary spherocytosis with novel SPTB gene mutations and hyperjaundice:A case report

BACKGROUND The aim of the present study was to enhance understanding of the diagnosis and treatment of atypical hereditary spherocytosis(HS),and to broaden the diagnostic thoughts of physicians for patients with jaundice.CASE SUMMARY A 28-year-old male presented with jaundice,bile duct stone,and splenomegaly,but without anemia.Other causes of jaundice were excluded,and gene se-quencing revealed a novel heterozygous variant of c.1801C>T(p.Q601X)in exon 14 of the SPTB(NM_01355436)gene on chromosome 14(chr14:65260580)in the patient’s blood;the biological parents and child of the patient did not have similar variants.A splenectomy was performed on the patient and his bilirubin levels returned to normal after surgery.Thus,a novel gene variant causing HS was identified.This variant may result in the truncation ofβ-hemoglobin in the erythrocyte membrane,leading to loss of normal function,jaundice,and hemolytic anemia.The clinical manifestations of the patient were hyperjaundice and an absence of typical hemolysis during the course of the disease,which caused challenges for diagnosis by the clinicians.CONCLUSION Following a definitive diagnosis,genetic testing and response to treatment identified a gene variant site for a novel hemolytic anemia.

Novel gene mutation in maturity-onset diabetes of the young:A case report

BACKGROUND Maturity-onset diabetes of the young(MODY)is the most common monogenic type of diabetes.Recently,14 gene mutations have been found to be associated with MODY.In addition,the KLF11 gene mutation is the pathogenic gene of MODY7.To date,the clinical and functional characteristics of the novel KLF11mutation c.G31A have not yet been reported.CASE SUMMARY We report of a 30-year-old male patient with a one-year history of nonketosisprone diabetes and a 3-generation family history of diabetes.The patient was found to carry a KLF11 gene mutation.Therefore,the clinical data of family members were collected and investigated.A total of four members of the family were found to have heterozygous mutations in the KLF11 gene c.G31A,which resulted in a change in the corresponding amino acid p.D11N.Three patients had diabetes mellitus,and one patient had impaired glucose tolerance.CONCLUSION The heterozygous mutation of the KLF11 gene c.G31A(p.D11N)is a new mutation site of MODY7.Subsequently,the main treatment included dietary interventions and oral drugs.

ADAMTS3 and FLT4 gene mutations result in congenital lymphangiectasia in newborns:A case report

BACKGROUND Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels.Congenital lymphangiectasia can affect various organ systems;however,it frequently occurs in the lungs accompanied with unexplained pleural effusion.Further,it might not be diagnosed during prenatal examination owing to the absence of pronounced abnormalities.However,after birth the newborn rapidly develops respiratory distress that quickly deteriorates.Genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of this disease.We report a rare case of heterozygous mutation of ADAMTS3 and FLT4 genes,which have not been reported previously.CASE SUMMARY We analysed the case of a neonate who had presented with only pleural effusion at a late gestational age and eventually died due to its inability to establish spontaneous breathing after birth.An autopsy revealed lymphangiectasia of the organ systems.Further,whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes,ADAMTS3 and FLT4,and Sanger verification revealed similar lesions in the mother with no symptoms.CONCLUSION Considering the presented case,obstetricians should observe unexplained foetal pleural effusion,and perform pathology analysis and whole exome sequencing for a conclusive diagnosis and prompt treatment.

Prevalence of Myocilin Gene Mutation in Adult-Onset Primary Open Angle Glaucoma and Non-Glaucoma Subjects Who Are Indigenes of Rivers State, Nigeria

Background: Glaucoma is the leading cause of irreversible blindness incapacitating over 80 million people worldwide. Several pathogenetic mechanisms have been postulated to explain the optic nerve damage that occur in POAG among which genetic predisposition is prominent. Gene-Linkage-based studies have identified genes associated with POAG: Myocilin, Optineurin, WDR36, Tank-Binding Kinase (TBK1) and APbb-2. Objective: To investigate the prevalence of myocilin gene mutation in adult-onset POAG patients and non-glaucoma subjects who are indigenes of Rivers State. Methodology: In this comparative cross-sectional study, 393 POAG patients attending the Glaucoma Clinic of UPTH were compared with 393 age and sex-matched phenotypically normal participants. Clinical assessment combined with findings from clinical records was used. Venous blood was obtained for genomic analyses. Extracted DNA was sequenced with specific primers for myocilin and polymerase chain reaction. Zymo-Bead Genomic DNA kit protocol was used to detect allelic differences. Results: Total of 786 participants participated in the study. The mean age was 59.8 ± 11.8 years. The prevalence of myocilin gene mutation (MYOC) in the study population was 5.3%, in the POAG group was 8.4%, and 2.3% in the non-glaucoma group. This observed difference was statistically significant (p = 0.001). Location of the mutant myocilin gene was in GLC1A 171638779, 171638703, 171638610 and 171638608. Conclusion: Mutations in myocilin gene are associated with adult-onset POAG in Rivers State. Its relevance as a biomarker for diagnosis of adult-onset POAG needs further investigations.

Analysis of EGFR gene mutations in lung adenocarcinoma in Karamay,Xinjiang,China

Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay,Xinjiang,China.Methods:Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019,and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction(Amplification RefractoryMutation System–PCR)method.The relationships between themutation types,mutation incidence,and clinical features were analyzed.Results:Of the 170 patients with lung adenocarcinoma,83 had EGFR mutations.The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%,which included mutations in exons 18(1.2%[2/170]),19(19.4%[33/170]),20(2.4%[4/170]),and 21(20.6%[35/170]).Intriguingly,there was a case with 9 mutations in exons 20 and 21.The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750.The main mutation in exon 21 was L858R(91.4%[32/35]).There was no significant difference in exons 19 and 21 mutation rates(P>0.05).The mutation rate of EGFR in female patients was significantly higher than that in male patients(P<0.05)but had no correlation with the age,smoking status,and clinical stage of patients with non–small cell lung cancer(P>0.05).The EGFR mutation rate may be related to the degree of tumor differentiation.Conclusions:Among patients with lung adenocarcinoma in Kelamayi(city in Xinjiang),EGFR mutations were more frequently detected in female patients,and the main sites of mutations were exons 19 and 21.

Relations of Budd-Chiari syndrome to prothrombin gene mutation

BACKGROUND: Budd-Chiari syndrome (BCS) is a type of disease characterized by portal hypertension and/or hy- pertension of the inferior vena cava (IVC) due to the ob- struction of the hepatic veins (HV) and/or intrahepatic IVC outlet. Being etiologically complicated and obscure, BCS can be acquired or idiopathic and several gene muta- tions may be contributable. This study was to explore whether prothrombin gene mutation (F G20210A) takes part in the pathogenesis of BCS and to investigate their cor- relativity. METHODS: In 38 proven BCS patients and 70 controls, polymerase chain reaction-restriction fragment length poly- morphism (PCR-RFLP) was used to find F G20210A mutation. To detect whether there are any mutations, four steps were taken: purification of genome DNA from whole blood, amplification of special fragment by polymerase chain reaction, digestion of the fragment via restriction en- donuclease, and analysis of results by polyacrylamide gel electrophoresis. RESULTS: F G20210A mutation was not detected in all patients and controls. CONCLUSIONS: No F G20210A mutation exists in Chi- nese patients with BCS, nor correlativity between the oc- currence of BCS and F G20210A mutation. The etiology of BCS in the Chinese needs further investigation.

Genetic aberration in primary hepatocellular carcinoma:correlation between p53 gene mutation and loss-of-heterozygosity on chromosome 16q21-q23 and 9p21-p23

To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular

Nonalcoholic fatty liver disease and HFE gene mutations:A Polish study

AIM:To describe a Polish population with nonalcoholic fatty liver disease(NAFLD)with regard to HFE gene mutations,as well as analyzing demographic and clinical data.METHODS:Sixty-two consecutive patients with biopsy-proven NAFLD were included in the study.Demographic,clinical,and laboratory data were summarized in a database.C282Y and H63D mutations of the HFE gene were analyzed using polymerase chain reactionrestriction fragment lenght polymorphism.RESULTS:The analyzed cohort consisted of 62 homo-geneic Caucasian participants,66.1%men and 33.9% women,with a median age of 48 years.The median body mass index was 29.05 kg/m 2 .Hypercholesterolemia was observed in 74.2%of patients and hypertriglyceridemia in 32.2%;16.1%had type 2 diabetes mellitus(DMt2).On liver biopsy,22.6%of NAFLD patients were found to have severe fibrosis.There were no differences between frequencies of HFE gene mutations in subgroups of NAFLD patients with less and more severe liver fibrosis.Obesity,older age,female gender and DMt2 were associated with more advanced fibrosis in this Polish cohort,as well as higher glucose level,serum iron and transaminase aspartate aminotransferase/alanine aminotransferase ratio.CONCLUSION:HFE mutations conferred no additional hepatic fibrosis risk in NAFLD,but higher serum iron was a risk factor for severe liver damage in NAFLD,regardless of HFE mutations.

Clinical Characteristics and Gene Mutation Analysis of Methylmalonic Aciduria

Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor adenosylcobalamin（cbl complementation groups）.The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry（GC-MS）,and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions（exon 2-13） and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424AG（p.T142A）,c.786TG（p.S262R）,c.808GC（p.G270R）,c.1323_1324insA,c.1445-1GA and c.1676＋77AC were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682CT（p.R228X） and c.323GA（p.R108H） were also found in this study.In addition,six previously described single nucleotide polymorphism（SNP）,c.636AG（p.K212K）,c.1495GA（p.A499T）,c.1595AG（p.H532R）,c.1992GA（p.A664A）,c.2011GA（p.V671I） and c.1677-53AG were identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.

Iron overload and HFE gene mutations in Polish patients with liver cirrhosis

BACKGROUND:Increased liver iron stores may contribute to the progression of liver injury and fibrosis,and are associated with a higher risk of hepatocellular carcinoma development.Pre-transplant symptoms of iron overload in patients with liver cirrhosis are associated with higher risk of infectious and malignant complications in liver transplant recipients.HFE gene mutations may be involved in the pathogenesis of liver iron overload and influence the progression of chronic liver diseases of different origins.This study was designed to determine the prevalence of iron overload in relation to HFE gene mutations among Polish patients with liver cirrhosis.METHODS:Sixty-one patients with liver cirrhosis included in the study were compared with a control group of 42 consecutive patients subjected to liver biopsy because of chronic liver diseases.Liver function tests and serum iron markers were assessed in both groups.All patients were screened for HFE mutations (C282Y,H63D,S65C).Thirty-six of 61 patients from the study group and all controls had liver biopsy performed with semiquantitative assessment of iron deposits in hepatocytes.RESULTS:The biochemical markers of iron overload and iron deposits in the liver were detected with a higher frequency (70% and 47% respectively) in patients with liver cirrhosis.There were no differences in the prevalence of all HFE mutations in both groups.In patients with a diagnosis of hepatocellular carcinoma,no significant associations with iron disorders and HFE gene mutations were found.CONCLUSIONS:Iron disorders were detected in patients with liver cirrhosis frequently but without significant association with HFE gene mutations.Only the homozygous C282Y mutation seems to occur more frequently in the selected population of patients with liver cirrhosis.As elevated biochemical iron indices accompanied liver iron deposits more frequently in liver cirrhosis compared to controls with chronic liver disease,there is a need for more extensive studies searching for the possible influence of non-HFE iron homeostasis regulators and their modulation on the course of chronic liver disease and liver cirrhosis.

GyrA and ParC Gene Mutation of Clinically Isolated Fluoroquinolones-resistant Strain of Salmonella

Nine strains resistant to five fluoroquinolones （Ciprofloxacin, Ofloxacin, Enrofloxacin, Danofloxacin, Sarafloxacin） were isolated from clinical samples and extracted the chromosomal DNA of these strains. Designed primers to amplify the Quinolone-resistance-determining region （QRDR） of gyrA and par（？,, then the PCR products were sequenced and analyzed. In comparision with NCTC5776, a single mutation was found at base 371 in gyrA of strain 38 which changed from C to T, and a single mutation was found at base 350 in gyrA of strain 60 which changed from A to C. No mutation was found in gyrA of the rest The mutation of strain 38 led to an amino acid substitution of Arg99Cys and the mutation of 60 led to an amino acid substitution of Met 92 Leu. No mutation was found in parC QRDR of all the isolates. These results indicats that the DNA gyrase will be the primary target to salmonella of fluoroquinolone.

Clinical manifestations and gene mutation in a case of Machado-Joseph disease

This study reports a case of a 75-year-old female Machado-Joseph disease patient exhibiting unstable walking and inaccurate hand holding for 8 months, which progressively worsened. Physical examination on admission showed cerebellar ataxia and a history of hypertension. Crania MRI demonstrated cerebellar and brain stem atrophy. Gene analysis showed abnormal amplification of the CAG trinucleotide repeat in exon 10 of the ataxin-3 （ATXN3） gene, resulting in 70-81 CAG repeats in the patient, with a significant positive family history.

Molecular diagnosis of 5α-reductase-2 gene mutation in two Indian families with male pseudohermaphroditism

Aim： To identify the genotype of two Indians with male pseudohermaphroditism. Methods： Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carded out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5α- reductase type 2 gene （SRDSA2） gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus. Results： We found an SRDSA2 gene mutation in exon 5, where arginine is substituted with glutamine （R246Q）, in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India. Conclusion： Identification of the R246Q mutation of the SRDSA2 gene from two unrelated Indian families possibly extends the founder gene effect.

The Role of Ras Gene Mutation in Gastric Cancer and Precancerous Lesions

Abnormality of ras gene family was studied in a total of 206 cases of gastric cancer and precancerous lesions by PCR-RFLP, PCR-SSCP and DNA sequencing. The results showed that mutation rate of H-ras 12 codon in metaplasia,atypical hyperplasia, early-stage cancer and advanced cancer was 16. 7%, 31. 2 %, 50. 0%, and 32. 2%, respectively. In the groups of superficial gastritis and normal controls, no mutation were detected in codon 12 of ras. Mutations of Hras 61 codon and N-ras 12 codon in various groups were the same as those in normal control. K-ras 12 codon mutation was detected in only 2 cases of gastric cancer by using PCR-SSCP, but it was not detected by DNA sequencing, which may be polymorphism. All H-ras 12 codon mutations were G→T mutation. There were significant difference between the groups of metaplasia, dysplasia, gastric carcinoma and normal control group (P<0.05, P<0.01, P<0.01,respectively). It was concluded that H-ras 12 codon mutation was an early event and may play an important role in gastric carcinogenesis. Although K-ras, N-ras mutation rates are high in colon cancer and leukemia, it seems to bear no relationship with gastric cancer.

P53 Gene Mutation and Expression of MDM2, P53,P16 Protein and their Relationship in Human Glioma

To investigate the effect of P53 protein accumulation and p53 gene mutation in the pathogenesis of glioma and to study the role of MDM2, P53 and P16 protein in glioma formation and progression and their relationship with each other, LSAB immunohistochemical staining method and non-isotopic PCR-SSCP techniques were used to detect the expression of MDM2, P53 and P16 protein and p53 gene mutation in 48 cases of gliomas. The results showed that the positive expression rate of MDM2, P53 and the negative rate of P16 was 22.9 %, 41.7 % and 60.4 %, respectively. The latter two in high grade （grade Ⅲ , Ⅳ） gliomas had a significantly higher rate than in the low grade （grade Ⅱ ） gliomas. Moreover, the co-expression of MDM2 and P53 protein was confirmed in only 1 of 48 cases. No significant difference was found in the rate of the expression of MDM2 between high grade and low grade gliomas （P〉0.1） . PCR-SSCP results showed that mutation of 5 --8 exons of p53 gene was detected in 17 out of 48 cases （35.42 %） . Mutation was detected in 16 of 20 cases of positive p53 expression, and another one was detected in 28 cases of negative expression cases. The correlation between p53 mutation and p53 immunopositivity was observed in 89.6 % of the cases. P53 gene mutation and the level of MDM2, P53 and PI6 protein were not related to age, gender of the patients, tumor location and size. It is concluded that the mutation of p53 and deletion of p16 might play important roles in the tumorigenesis of gliomas and it was significantly associated with the grade of tumor differentiation. P53 protein accumulation can indirectly reflect p53 mutation. MDM2 amplification and overexpression might be an early event in the growth of human gliomas.

Detection of ATP2C1 Gene Mutation in Familial Benign Chronic Pemphigus

Summary： The ATP2C1 gene mutation in one ease of familial benign chronic pemphigus was investigated.One patient was diagnosed as familial benign chronic pemphigus by pathology, ultrastructral examination and clinical features. Genomic DNA was extracted from blood samples. Mutation of ATP2CI gene was detected by polymerase chain reaction （PCR） and DNA sequencing. The results showed that deletion mutation was detected in ATP2C1 gene in this patient, which was 2374delTTTG. No mutation was found in the family members and normal individuals. It was coneluded that the 2374delTTTG mutation in ATP2C1 gene was the specific mutation for the clinical phenotype for this patient and was a de novo mutation.

Gene mutation analysis and immune checkpoint therapy in head and neck squamous cell carcinoma

Immune checkpoint inhibitors(ICI),represented by blocked programmed cell death-1(PD-1),is a group of novel medicines for anti-tumor immunotherapy.It has been approved by the U.S.Food and Drug Administration(FDA)in recent years for relapsed or metastatic head and neck squamous cell carcinoma(HNSCC),and brings promising treatment prospects.However,the instability caused by tumor gene mutations significantly compromises the therapeutic effect of ICI.Therefore,the identification and analysis of HNSCC gene mutations can further guide and optimize the application of ICIs in HNSCC.In this study,we preliminarily described the clinical research progress of ICI therapy and the potential immune escape mechanism in HNSCC.An overview of complete HNSCC gene mutation results was generated from the bioinformatics study of TCGA database to further explain and analyze the relevant molecular mechanisms,which may aid in designing future personalized therapeutic strategies for HNSCC patients.