AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histolo...AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage Ⅱ/Ⅲ CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected.Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3 CA and TP53 mutation status with overall survival(OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.RESULTS Among the 241 patients with stage Ⅱ/Ⅲ in this cohort, the PIK3 CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3 CA and TP53 double mutations. The PIK3 CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3 CA and TP53 mutations, those with double PIK3 CA-TP53 mutations showed a significantly worse survival(univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3 CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors(multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3 CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status(Log-rank P = 0.041)CONCLUSION Double mutation of PIK3 CA and TP53 is correlated with a shorter OS in stage Ⅱ/Ⅲ CRC patients treated with 5-fluorouracil-based therapy.展开更多
BACKGROUND Gastric cancer(GC)is a deadly tumor with the fifth highest occurrence and highest global mortality rates.Owing to its heterogeneity,the underlying mechanism of GC remains unclear,and chemotherapy offers lit...BACKGROUND Gastric cancer(GC)is a deadly tumor with the fifth highest occurrence and highest global mortality rates.Owing to its heterogeneity,the underlying mechanism of GC remains unclear,and chemotherapy offers little benefit to individuals.AIM To investigate the clinical outcomes of TP53 and CDH1 mutations in GC.METHODS In this study,202 gastric adenocarcinoma tumor tissues and their corresponding normal tissues were collected.A total of 490 genes were identified using target capture.Through t-test and Wilcoxon rank-sum test,somatic mutations,microsatellite instability,and clinical statistics,including overall survival,were detected,compared,and calculated.RESULTS The mutation rates of 32 genes,including TP53,SPEN,FAT1,and CDH1 exceeded 10%.TP53 mutations had a slightly lower overall occurrence rate(33%).The TP53 mutation rate was significantly higher in advanced stages(stage Ⅲ/Ⅳ)than that in early stages(stage Ⅰ/Ⅱ)(P<0.05).In contrast,CDH1 mutations were significantly associated with diffuse GC.TP53 is related to poor prognosis of advanced-stage tumors;nevertheless,CDH1 corresponds to a diffuse type of cancer.TP53 is exclusively mutated in CDH1 and is primarily affected by two distinct GC mechanisms.CONCLUSION Different somatic mutation patterns in TP53 and CDH1 indicate two major mechanisms of GC.展开更多
In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg.A common gene mutation in gastric cancer(GC)is the TP53 mutation.As a tumor suppressor gene,TP53 is implicated in...In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg.A common gene mutation in gastric cancer(GC)is the TP53 mutation.As a tumor suppressor gene,TP53 is implicated in more than half of all tumor occurrences.TP53 gene mutations in GC tissue may be related with clinical pathological aspects.The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy.CDH1 encodes E-cadherin,which is involved in cell-to-cell adhesion,epithelial structure maintenance,cell polarity,differentiation,and intracellular signaling pathway modulation.CDH1 mutations and functional loss can result in diffuse GC,and CDH1 mutations can serve as independent prognostic indicators for poor prognosis.GC patients can benefit from genetic counseling and testing for CDH1 mutations.Demethylation therapy may assist to postpone the onset and progression of GC.The investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations,as well as providing some basis for evaluating the prognosis of GC patients.展开更多
Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an i...Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.展开更多
Objectives:The tumorigenic progression of Lung adenocarcinoma(LUAD),the predominant NSCLC subtype,is predominantly driven by co-occurring mutations in KRAS proto-oncogene(KRAS)/Tumor protein p53(TP53).However,their im...Objectives:The tumorigenic progression of Lung adenocarcinoma(LUAD),the predominant NSCLC subtype,is predominantly driven by co-occurring mutations in KRAS proto-oncogene(KRAS)/Tumor protein p53(TP53).However,their impact on tumor microenvironment(TME)heterogeneity,particularly neutrophil dynamics,remains poorly understood.This present study aims to elucidate how KRAS/TP53 mutations reprogram the TME and develop a neutrophil-centric prognostic signature for LUAD.Methods:Leveraging single-cell RNA sequencing data and transcriptome data,neutrophil subpopulations were identified using Seurat and CellChat R packages,with trajectory analysis via Monocle2 R package.High-dimensional weighted gene co-expression network analysis(hdWGCNA),univariate Cox regression,and least absolute shrinkage and selection operator(LASSO)regression analyses were employed to generate a prognostic signature.Functional validation included Ras homolog family member V(RHOV)knockdown in A549/H1299 cells using siRNA,were assessed by cell counting kit 8(CCK8)assay,wound healing assay,and transwell assay.Results:KRAS/TP53-mutated LUAD exhibited increased neutrophil infiltration,particularly IS MUT subtypes with enhanced OSM/CALCR/IL-1 signaling.A five-gene prognostic signature(MS4A1,ANLN,FAM83A,RHOV,KRT6A)stratified patients into high-and low-risk groups with divergent overall survival in the TCGA-LUAD cohort(p<0.0001).AUCs achieved 0.73,0.70,and 0.66 at 1-,3-,and 5-year,respectively.External validation in immunotherapy cohorts(IMvigor210,GSE78220)confirmed the fine predictive capability of the prognostic signature in predicting treatment response.An integrated prognostic nomogram combining clinicopathological features and risk score further improved its clinical utility.Pseudotime analysis found that RHOV was essential for the growth of lung epithelial cells.RHOV knockdown significantly reduced the proliferation,migration,and invasion capabilities of A549/H1299 cells in vitro.Conclusion:KRAS/TP53 mutations may drive neutrophil heterogeneity in the TME of LUAD,addressing prognostic and therapeutic value.The five-gene signature and RHOV targeting offer translational relevance for risk stratification and therapy.These findings bridge genomic alterations with TME remodeling,advancing precision oncology in LUAD.展开更多
Alzheimer’s disease (AD) leads to the generation of β-amyloid (Aβ), which may damage DNA and thus lead to apoptosis induction by the p53 pathway. Dysfunction of the p53 protein may then be connected with the develo...Alzheimer’s disease (AD) leads to the generation of β-amyloid (Aβ), which may damage DNA and thus lead to apoptosis induction by the p53 pathway. Dysfunction of the p53 protein may then be connected with the development of AD. Studies were conducted on 28 AD patients and 30 non-AD controls. Analysis of TP53 mutations in exon 7 was performed on DNA isolated from whole blood and biochemical parameters in the peripheral lymphocytes of these individuals. Our study showed a silent mutation TP53 C708T (21%) [p TP53 C748A (4%) only in the AD patients. Moreover, in AD patients with the TP53 C748A mutation, the level of 8-oxo-2’- deoxyguanosine (8-oxo2dG) was more than 5 times higher than the average level in this study group. In AD patients with the wild-type TP53 gene, the level of 8-oxo2dG was correlated with the level of protein p53 (R = +0.7388, p TP53 (p TP53 (C748A, C708T) may be associated with pathogenesis of AD.展开更多
P53 gene mutations have been known to be highly related to the majority of human cancers.The colocation of biologists and bioinformaticians have constructed many databases for cancer research.Although the relationship...P53 gene mutations have been known to be highly related to the majority of human cancers.The colocation of biologists and bioinformaticians have constructed many databases for cancer research.Although the relationship between the presence of TP53 mutation and cancers has been reported in various studies,few reports TP53 mutation distribution in different functional domains.Hence,we use 2 databases(The TP53 Mutation Database of the International Agency for the Research on Cancer and The Genomic Data Commons data portal)to compare survival rate with and without TP53 mutations in a certain cancer,as well as to find most frequent mutation sites in different functional domains of the TP53 protein.Our study shows that most somatic mutations of TP53 and high mutation rate sites are concentrated in the DNA-binding domain,and the survival of certain cancers varies with and without P53.展开更多
As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer of...As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.展开更多
AIMS To examine the prevalance of p53 mutations in hepatocellular carcinoma (HCC) from Chongqing area and the relationship between the p53 mutations and clinicopathological features of HCC,as well as the risk factors....AIMS To examine the prevalance of p53 mutations in hepatocellular carcinoma (HCC) from Chongqing area and the relationship between the p53 mutations and clinicopathological features of HCC,as well as the risk factors. METHODS The overexpression and point mutations of tumor suppressor gene p53 in 38 cases of HCC were detected by a sensitive antigen retrieval fluid (ARF) immunohistochemical method and polymerase chain re- action(PCR)-restriction fragment length polymorphism (RFLP),and single strand conformation polymorphism (SSCP)-silver staining analysis. RESULTS The results showed that 16 of 38 HCCs had positive p53 protein (42.1%),7 HCCs had p53 mutation at 249 (18.4 % ) and 2 HCCS had point muta- tion within exon 7 other than 249. Among 9 cases of HCC with mutations,8 cases demonstrated positive p53 protein,its coincidental rate was 88.9%. The overexpression and mutations of p53 were significantly related to the differentiation and metastasis of HCCs. The frequency of p53 mutations was consistent with high prevalence of HBV and a moderate aflatoxin B1 (AFB1) exposure in our area. CONCLUSIONS The results suggest that AFB1 acts synergistically with HBV in the generation of p53 mutations. Furthermore,dietary exposure to AFB1 may mainly contribute to the tumor specific mutation at codon 249,while HBV may account for other scattered mutations in HCC.展开更多
AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such...AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such as macroscopic classifica- tion,stage,degree of differentiation,depth of tumour invasion and lymphonod metastasis.Tamura has reported that p53 gene mutations mainly occur in the aneuploid tumours.But in China, nothing is reported in this field of study.Our aim is to analyze the relationship between p53 gene mutations and these param- eters including DNA ploidy in Chinese primary gasrtic cancers. METHODS Mutations of the p53 gene in exon5-8 were examined in 20 cases of primary gasric cancer by PCR-SSCP (Polymerase-chain-reaction-single-strand-conforma- tion-polymorphism)analysis. RESULTS Mutations were detected in 8(40%)cases:2 cases in exon5-6,2 cases in exon7,4 cases in exon8.These mutations were detected from stage 0 to stage Ⅲ No significant association was found between p53 gene mutations and the clinicopathological parameters such as macroscopic classifico- tion,degree of histological differentiation,depth of tumour in- vasion and lymphonod metastasis.In addition,66.7%(6 of 9) of aneuploid tumours had p53 mutations and only 18.2%(2 of 11)of diploid tumours had mutations. CONCLUSIONS These results suggest that p53 gene muta- tions are related to DNA ploidy alterations and that p53 gene is one of the important turnout suppressor genes in human gastric cancer.展开更多
p53免疫组化与TP53突变状态之间的关系一直存在争议。本组研究重新评估p53免疫组化提示TP53突变状态的价值。通过外显子测序,共检测了157例弥漫型胶质瘤（ WHO Ⅱ～Ⅳ级）冷冻组织的TP53基因第4～10外显子。对应所有病例的福尔马林固定...p53免疫组化与TP53突变状态之间的关系一直存在争议。本组研究重新评估p53免疫组化提示TP53突变状态的价值。通过外显子测序,共检测了157例弥漫型胶质瘤（ WHO Ⅱ～Ⅳ级）冷冻组织的TP53基因第4～10外显子。对应所有病例的福尔马林固定石蜡包埋组织检测p53免疫组化（克隆号DO-7）,评估表达强度和比率。66例突变病例中发现72个突变,包括60个错义突变,5个无义突变,4个缺失和3个剪切位点变异。通过 ROC曲线分析发现大于10%的肿瘤细胞强阳性可最大程度地提示突变。展开更多
基金Supported by the National Natural Science Foundation of China,No.81272480Science and Technology Commi-ssion of Shanghai Municipality,No.15411969900 and No.16DZ2342200
文摘AIM To investigate the predictive value of PIK3 CA and TP53 mutation status in colorectal cancer(CRC) patients treated with 5-fluorouracil-based chemotherapy.METHODS In this study, a total of 315 patients with histologically proven CRC were enrolled from Yangpu Hospital affiliated to Shanghai Tongji University between 2007 and 2011. Of these patients, 241 with stage Ⅱ/Ⅲ CRC received 5-fluorouracil-based adjuvant chemotherapy. Formalin-fixed paraffin-embedded lesion samples of the patients with curatively resected CRC were collected.Next-generation sequencing was performed to identify somatic gene mutations. The correlation of PIK3 CA and TP53 mutation status with overall survival(OS) was analyzed using a Cox proportional hazard model and the Kaplan-Meier method.RESULTS Among the 241 patients with stage Ⅱ/Ⅲ in this cohort, the PIK3 CA and/or TP53 mutation was detected in 177 patients, among which 54 patients had PIK3 CA and TP53 double mutations. The PIK3 CA or TP53 mutation was not significantly correlated with OS in univariate and multivariate analyses. Compared with patients without PIK3 CA and TP53 mutations, those with double PIK3 CA-TP53 mutations showed a significantly worse survival(univariate HR = 2.21; 95%CI: 1.15-4.24; multivariate HR = 2.02; 95%CI: 1.04-3.91). The PIK3 CA mutation located in the kinase domain showed a trend toward a shorter OS compared with wild-type tumors(multivariate HR = 1.56; 95%CI: 1.00-2.44; P = 0.052). The Kaplan-Meier curve showed that patients harboring the PIK3 CA mutation located in the kinase domain had a worse clinical outcome than those with wild-type status(Log-rank P = 0.041)CONCLUSION Double mutation of PIK3 CA and TP53 is correlated with a shorter OS in stage Ⅱ/Ⅲ CRC patients treated with 5-fluorouracil-based therapy.
基金Supported by Guangdong Yiyang Healthcare Charity Foundation,No.JZ2022014.
文摘BACKGROUND Gastric cancer(GC)is a deadly tumor with the fifth highest occurrence and highest global mortality rates.Owing to its heterogeneity,the underlying mechanism of GC remains unclear,and chemotherapy offers little benefit to individuals.AIM To investigate the clinical outcomes of TP53 and CDH1 mutations in GC.METHODS In this study,202 gastric adenocarcinoma tumor tissues and their corresponding normal tissues were collected.A total of 490 genes were identified using target capture.Through t-test and Wilcoxon rank-sum test,somatic mutations,microsatellite instability,and clinical statistics,including overall survival,were detected,compared,and calculated.RESULTS The mutation rates of 32 genes,including TP53,SPEN,FAT1,and CDH1 exceeded 10%.TP53 mutations had a slightly lower overall occurrence rate(33%).The TP53 mutation rate was significantly higher in advanced stages(stage Ⅲ/Ⅳ)than that in early stages(stage Ⅰ/Ⅱ)(P<0.05).In contrast,CDH1 mutations were significantly associated with diffuse GC.TP53 is related to poor prognosis of advanced-stage tumors;nevertheless,CDH1 corresponds to a diffuse type of cancer.TP53 is exclusively mutated in CDH1 and is primarily affected by two distinct GC mechanisms.CONCLUSION Different somatic mutation patterns in TP53 and CDH1 indicate two major mechanisms of GC.
基金Supported by the Youth Development Fund Task Book of the First Hospital of Jilin University,No.JDYY13202210.
文摘In this editorial we comment on an article published in a recent issue of the World J Gastrointest Surg.A common gene mutation in gastric cancer(GC)is the TP53 mutation.As a tumor suppressor gene,TP53 is implicated in more than half of all tumor occurrences.TP53 gene mutations in GC tissue may be related with clinical pathological aspects.The TP53 mutation arose late in the progression of GC and aided in the final switch to malignancy.CDH1 encodes E-cadherin,which is involved in cell-to-cell adhesion,epithelial structure maintenance,cell polarity,differentiation,and intracellular signaling pathway modulation.CDH1 mutations and functional loss can result in diffuse GC,and CDH1 mutations can serve as independent prognostic indicators for poor prognosis.GC patients can benefit from genetic counseling and testing for CDH1 mutations.Demethylation therapy may assist to postpone the onset and progression of GC.The investigation of TP53 and CDH1 gene mutations in GC allows for the investigation of the relationship between these two gene mutations,as well as providing some basis for evaluating the prognosis of GC patients.
基金supported by the National Natural Science Foundation of China(32171131,32371013,82071429,82471274,and 32371181)Shandong Province Natural Science Foundation(2021ZDSYS11,ZR2019ZD31,and ZR2022MC098)the Taishan Scholars Construction Project.
文摘Iron metabolism is a critical factor in tumorigenesis and development. Although TP53 mutations are prevalent in glioblastoma (GBM), the mechanisms by which TP53 regulates iron metabolism remain elusive. We reveal an imbalance iron homeostasis in GBM via TCGA database analysis. TP53 mutations disrupted iron homeostasis in GBM, characterized by elevated total iron levels and reduced ferritin (FTH). The gain-of-function effect triggered by TP53 mutations upregulates itchy E3 ubiquitin-protein ligase (ITCH) protein expression in astrocytes, leading to FTH degradation and an increase in free iron levels. TP53-mut astrocytes were more tolerant to the high iron environment induced by exogenous ferric ammonium citrate (FAC), but the increase in intracellular free iron made them more sensitive to Erastin-induced ferroptosis. Interestingly, we found that Erastin combined with FAC treatment significantly increased ferroptosis. These findings provide new insights for drug development and therapeutic modalities for GBM patients with TP53 mutations from iron metabolism perspectives.
基金supported by Zhongnanshan Medical Foundation of Guangdong Province(No.ZNSXS-20240108 to Anping Xu).
文摘Objectives:The tumorigenic progression of Lung adenocarcinoma(LUAD),the predominant NSCLC subtype,is predominantly driven by co-occurring mutations in KRAS proto-oncogene(KRAS)/Tumor protein p53(TP53).However,their impact on tumor microenvironment(TME)heterogeneity,particularly neutrophil dynamics,remains poorly understood.This present study aims to elucidate how KRAS/TP53 mutations reprogram the TME and develop a neutrophil-centric prognostic signature for LUAD.Methods:Leveraging single-cell RNA sequencing data and transcriptome data,neutrophil subpopulations were identified using Seurat and CellChat R packages,with trajectory analysis via Monocle2 R package.High-dimensional weighted gene co-expression network analysis(hdWGCNA),univariate Cox regression,and least absolute shrinkage and selection operator(LASSO)regression analyses were employed to generate a prognostic signature.Functional validation included Ras homolog family member V(RHOV)knockdown in A549/H1299 cells using siRNA,were assessed by cell counting kit 8(CCK8)assay,wound healing assay,and transwell assay.Results:KRAS/TP53-mutated LUAD exhibited increased neutrophil infiltration,particularly IS MUT subtypes with enhanced OSM/CALCR/IL-1 signaling.A five-gene prognostic signature(MS4A1,ANLN,FAM83A,RHOV,KRT6A)stratified patients into high-and low-risk groups with divergent overall survival in the TCGA-LUAD cohort(p<0.0001).AUCs achieved 0.73,0.70,and 0.66 at 1-,3-,and 5-year,respectively.External validation in immunotherapy cohorts(IMvigor210,GSE78220)confirmed the fine predictive capability of the prognostic signature in predicting treatment response.An integrated prognostic nomogram combining clinicopathological features and risk score further improved its clinical utility.Pseudotime analysis found that RHOV was essential for the growth of lung epithelial cells.RHOV knockdown significantly reduced the proliferation,migration,and invasion capabilities of A549/H1299 cells in vitro.Conclusion:KRAS/TP53 mutations may drive neutrophil heterogeneity in the TME of LUAD,addressing prognostic and therapeutic value.The five-gene signature and RHOV targeting offer translational relevance for risk stratification and therapy.These findings bridge genomic alterations with TME remodeling,advancing precision oncology in LUAD.
文摘Alzheimer’s disease (AD) leads to the generation of β-amyloid (Aβ), which may damage DNA and thus lead to apoptosis induction by the p53 pathway. Dysfunction of the p53 protein may then be connected with the development of AD. Studies were conducted on 28 AD patients and 30 non-AD controls. Analysis of TP53 mutations in exon 7 was performed on DNA isolated from whole blood and biochemical parameters in the peripheral lymphocytes of these individuals. Our study showed a silent mutation TP53 C708T (21%) [p TP53 C748A (4%) only in the AD patients. Moreover, in AD patients with the TP53 C748A mutation, the level of 8-oxo-2’- deoxyguanosine (8-oxo2dG) was more than 5 times higher than the average level in this study group. In AD patients with the wild-type TP53 gene, the level of 8-oxo2dG was correlated with the level of protein p53 (R = +0.7388, p TP53 (p TP53 (C748A, C708T) may be associated with pathogenesis of AD.
文摘P53 gene mutations have been known to be highly related to the majority of human cancers.The colocation of biologists and bioinformaticians have constructed many databases for cancer research.Although the relationship between the presence of TP53 mutation and cancers has been reported in various studies,few reports TP53 mutation distribution in different functional domains.Hence,we use 2 databases(The TP53 Mutation Database of the International Agency for the Research on Cancer and The Genomic Data Commons data portal)to compare survival rate with and without TP53 mutations in a certain cancer,as well as to find most frequent mutation sites in different functional domains of the TP53 protein.Our study shows that most somatic mutations of TP53 and high mutation rate sites are concentrated in the DNA-binding domain,and the survival of certain cancers varies with and without P53.
基金supported by the National Natural Science Foun-dation of China(grant numbers 81974483 and 82072589)the ChineseSocietyofClinicalOncology-HengruiCancerResearch Fund(Y-HR2020QN-0946).
文摘As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.
文摘AIMS To examine the prevalance of p53 mutations in hepatocellular carcinoma (HCC) from Chongqing area and the relationship between the p53 mutations and clinicopathological features of HCC,as well as the risk factors. METHODS The overexpression and point mutations of tumor suppressor gene p53 in 38 cases of HCC were detected by a sensitive antigen retrieval fluid (ARF) immunohistochemical method and polymerase chain re- action(PCR)-restriction fragment length polymorphism (RFLP),and single strand conformation polymorphism (SSCP)-silver staining analysis. RESULTS The results showed that 16 of 38 HCCs had positive p53 protein (42.1%),7 HCCs had p53 mutation at 249 (18.4 % ) and 2 HCCS had point muta- tion within exon 7 other than 249. Among 9 cases of HCC with mutations,8 cases demonstrated positive p53 protein,its coincidental rate was 88.9%. The overexpression and mutations of p53 were significantly related to the differentiation and metastasis of HCCs. The frequency of p53 mutations was consistent with high prevalence of HBV and a moderate aflatoxin B1 (AFB1) exposure in our area. CONCLUSIONS The results suggest that AFB1 acts synergistically with HBV in the generation of p53 mutations. Furthermore,dietary exposure to AFB1 may mainly contribute to the tumor specific mutation at codon 249,while HBV may account for other scattered mutations in HCC.
文摘AIMS p53 gene is one of the focuses in the study of tu- mour suppressor genes.So far,there is still controversy about the relationship between p53 alterations and clinicolpathological parameters of gastic cancers such as macroscopic classifica- tion,stage,degree of differentiation,depth of tumour invasion and lymphonod metastasis.Tamura has reported that p53 gene mutations mainly occur in the aneuploid tumours.But in China, nothing is reported in this field of study.Our aim is to analyze the relationship between p53 gene mutations and these param- eters including DNA ploidy in Chinese primary gasrtic cancers. METHODS Mutations of the p53 gene in exon5-8 were examined in 20 cases of primary gasric cancer by PCR-SSCP (Polymerase-chain-reaction-single-strand-conforma- tion-polymorphism)analysis. RESULTS Mutations were detected in 8(40%)cases:2 cases in exon5-6,2 cases in exon7,4 cases in exon8.These mutations were detected from stage 0 to stage Ⅲ No significant association was found between p53 gene mutations and the clinicopathological parameters such as macroscopic classifico- tion,degree of histological differentiation,depth of tumour in- vasion and lymphonod metastasis.In addition,66.7%(6 of 9) of aneuploid tumours had p53 mutations and only 18.2%(2 of 11)of diploid tumours had mutations. CONCLUSIONS These results suggest that p53 gene muta- tions are related to DNA ploidy alterations and that p53 gene is one of the important turnout suppressor genes in human gastric cancer.
文摘p53免疫组化与TP53突变状态之间的关系一直存在争议。本组研究重新评估p53免疫组化提示TP53突变状态的价值。通过外显子测序,共检测了157例弥漫型胶质瘤（ WHO Ⅱ～Ⅳ级）冷冻组织的TP53基因第4～10外显子。对应所有病例的福尔马林固定石蜡包埋组织检测p53免疫组化（克隆号DO-7）,评估表达强度和比率。66例突变病例中发现72个突变,包括60个错义突变,5个无义突变,4个缺失和3个剪切位点变异。通过 ROC曲线分析发现大于10%的肿瘤细胞强阳性可最大程度地提示突变。
