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1.
Article in Chinese | WPRIM | ID: wpr-879520

ABSTRACT

OBJECTIVE@#To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function.@*METHODS@#Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization.@*RESULTS@#The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene.@*CONCLUSION@#The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.


Subject(s)
DNA Mutational Analysis , Female , Frameshift Mutation , HEK293 Cells , HeLa Cells , Humans , Male , Pedigree , Polycystic Kidney, Autosomal Dominant/physiopathology , Protein Kinases/genetics , Protein Transport/genetics , Whole Exome Sequencing
2.
Article in Chinese | WPRIM | ID: wpr-879503

ABSTRACT

OBJECTIVE@#To detect potential variant in a male neonate affected with congenital nephrogenic diabetes insipidus (CNDI).@*METHODS@#Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the child and his parents. The whole coding regions of the arginine vasopressin V2 receptor (AVPR2) gene were amplified by PCR and subjected to Sanger sequencing.@*RESULTS@#The patient presented recurrent fever and polyuria after birth. Multiple blood gas analyses indicated hypernatremia. Ultrasound showed bilateral hydronephrosis and hydroureter. The patient was partially responsive to hydrochlorothiazide. DNA analysis identified a hemizygous frameshift variant c.890-899delACCCGGAGGC in exon 2 of the AVPR2 gene in the proband. His mother was heterozygous for the same variant.@*CONCLUSION@#The c.890-899delACCCGGAGGC variant of the AVPR2 gene probably underlies the CNDI in the child. Above discovery has enriched to spectrum of CNDI associated variants.


Subject(s)
Adult , Diabetes Insipidus, Nephrogenic/genetics , Exons , Female , Frameshift Mutation , Humans , Hydrochlorothiazide/therapeutic use , Infant, Newborn , Male , Pedigree , Receptors, Vasopressin/genetics
3.
Article in Chinese | WPRIM | ID: wpr-879915

ABSTRACT

OBJECTIVE@#To identify the genetic causes of a family with lymphedema-distichiasis syndrome (LDS).@*METHODS@#The whole exome sequencing was performed in a aborted fetus as the proband, and a candidate gene was identified. Peripheral blood of 8 family members were collected. Genotypic-phenotypic analysis were carried out through PCR amplification and Sanger sequencing.@*RESULTS@#The proband, and the mother, grandmother, uncle, granduncle of the proband all had distichiasis or varix of lower limb carried a @*CONCLUSIONS@#The


Subject(s)
Aborted Fetus/physiopathology , Adult , Eyelashes/pathology , Female , Forkhead Transcription Factors/genetics , Frameshift Mutation , Humans , Lymphedema/pathology , Male , Phenotype , Pregnancy , Whole Exome Sequencing
4.
Article in Chinese | WPRIM | ID: wpr-828313

ABSTRACT

OBJECTIVE@#To explore the molecular etiology for a Chinese family with mitochondrial DNA depletion syndrome.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patient and her parents.Targeted capture and next-generation sequencing was carried out to detect potential variants. Suspected variant was validated by Sanger sequencing.@*RESULTS@#A novel homozygous frameshift variant c.505_508delTATC was identified in the patient, for which both his mother and father were carriers.@*CONCLUSION@#The frameshift variant c.505_508delTATC probably underlies the mitochondrial DNA depletion syndrome in this patient. The result also enriched the variant spectrum of DGUOK gene.


Subject(s)
Asian Continental Ancestry Group , Genetics , DNA, Mitochondrial , Genetics , Female , Frameshift Mutation , Humans , Mutation , Phosphotransferases (Alcohol Group Acceptor) , Genetics , Syndrome
5.
Blood Research ; : 17-26, 2020.
Article in English | WPRIM | ID: wpr-820807

ABSTRACT

BACKGROUND: DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. CDKN2B plays an important role in the regulation of hematopoietic progenitor cells and DNMT3A mutation is associated with CDKN2B promoter methylation. We analyzed the characteristics of DNMT3A mutations including their clinical significance in AML and their influence on promoter methylation and CDKN2B expression.METHODS: A total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in DNMT3A, CEBPA, and NPM1 were analyzed by bidirectional Sanger sequencing. We evaluated CDKN2B promoter methylation and expression using pyrosequencing and RT-qPCR.RESULTS: We identified DNMT3A mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8–23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of CEBPA. There was no significant difference in CDKN2B promoter methylation according to the presence or type of DNMT3A mutations. CDKN2B expression inversely correlated with CDKN2B promoter methylation and was significantly higher in AML with R882H mutation in DNMT3A. We demonstrated that DNMT3A mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The DNMT3A mutation remained as the independent unfavorable prognostic factor after multivariate analysis.CONCLUSION: We characterized DNMT3A mutations in AML and revealed the association between the DNMT3A mutation and CDKN2B expression and clinical outcome.


Subject(s)
Adult , DNA Methylation , Exons , Frameshift Mutation , Hematopoietic Stem Cells , Humans , Leukemia, Myeloid, Acute , Methylation , Multivariate Analysis
6.
Article in English | WPRIM | ID: wpr-764509

ABSTRACT

The infantile convulsions and choreoathetosis (ICCA) syndrome is defined when two overlapping clinical features of benign familial infantile epilepsy (BFIE) and paroxysmal kinesigenic dyskinesia (PKD) are present in an individual or a family. Since the gene encoding proline-rich transmembrane protein 2 (PRRT2) was first identified in Han Chinese families with PKD, mutations of PRRT2 have additionally been reported in patients with BFIE and ICCA. We attempted to identify the genetic etiology in an ICCA family where the proband, her elder sister, and a maternal male cousin had BFIE, and her mother had PKD. Whole-exome sequencing performed in the proband and her sister and mother identified a novel pathogenic mutation of PRRT2 (c.640delinsCC; p.Ala214ProfsTer11), which was verified by Sanger sequencing. This frameshift PRRT2 mutation located near the genetic hot spot of base 649_650 results in the premature termination of the protein, as do most previously reported mutations in BFIE, ICCA, and PKD.


Subject(s)
Asian Continental Ancestry Group , Dyskinesias , Epilepsy , Frameshift Mutation , Humans , Male , Mothers , Seizures , Siblings
7.
Article in Chinese | WPRIM | ID: wpr-819040

ABSTRACT

OBJECTIVE@#To identify pathogenic mutation for a family with neurofibromatosis type 1(NF1) and provide prenatal diagnosis for them.@*METHODS@#Mutation analysis of the sporadic family with NF1 was performed with target captured next generation sequencing and Sanger sequencing. RNA samples were extracted from the lymphocytes of NF1 patient and her parents. RT-PCR and Sanger sequencing were performed to analyze the relative mRNA expression in the samples. Prenatal diagnosis of the pathogenic mutation was offered to the fetus.@*RESULTS@#A novel splicing mutation c.1260+4A>T in the gene was found in the proband of the family, but was not found in her parents.cDNA sequencing showed that 13 bases inserted into the 3' end of exon 11 in the gene lead to a frameshift mutation. Prenatal diagnosis suggested that the fetus did not carried the mutant.@*CONCLUSIONS@#The : c.1260+4A>T mutation found in the NF1 patient is considered to be pathogenic, which provides information for family genetic counseling and prenatal diagnosis.


Subject(s)
DNA Mutational Analysis , Female , Frameshift Mutation , Genetic Testing , Humans , Male , Neurofibromatosis 1 , Diagnosis , Genetics , Pregnancy , Prenatal Diagnosis
8.
Article in English | WPRIM | ID: wpr-760867

ABSTRACT

Waardenburg syndrome (WS) type IV is characterized by pigmentary abnormalities, deafness and Hirschsprung's disease. This syndrome can be triggered by dysregulation of the SOX10 gene, which belongs to the SOX (SRY-related high-mobility group-box) family of genes. We discuss the first known case of a SOX10 frameshift mutation variant defined as c.895delC causing WS type IV without Hirschsprung's disease. This female patient of unrelated Kuwaiti parents, who tested negative for cystic fibrosis and Hirschsprung's disease, was born with meconium ileus and malrotation and had multiple surgical complications likely due to chronic intestinal pseudo-obstruction. These complications included small intestinal necrosis requiring resection, development of a spontaneous fistula between the duodenum and jejunum after being left in discontinuity, and short gut syndrome. This case and previously reported cases demonstrate that SOX10 gene sequencing is a consideration in WS patients without aganglionosis but with intestinal dysfunction.


Subject(s)
Cystic Fibrosis , Deafness , Duodenum , Female , Fistula , Frameshift Mutation , Hirschsprung Disease , Humans , Ileus , Intestinal Pseudo-Obstruction , Jejunum , Meconium , Necrosis , Parents , Waardenburg Syndrome
9.
Article in Korean | WPRIM | ID: wpr-759588

ABSTRACT

D antigens are clinically significant, and routine tests on the D antigen requires the inclusion of weak D testing, which is performed using indirect antihuman immunoglobulin methods. On the other hand, exact typing of the D type of an individual can be done more precisely with RHD genotyping, which is a useful tool in cases where the RHD gene is intact. The majority of weak-D or partial-D cases are from single nucleotide changes or hybridization of RHD and RHCE genes. Nevertheless, frameshift mutations can also result in weak or partial-D. The characteristics of a frameshift mutation is typically a change in protein product after a problematic mutation and early termination of transcription, leading into truncated protein products. This paper reports a D-variant case with RHD 711delC along with a review of the relevant literature. In addition, the results of software analysis are reported.


Subject(s)
Frameshift Mutation , Genotype , Hand , Immunoglobulins
10.
Article in Chinese | WPRIM | ID: wpr-776813

ABSTRACT

OBJECTIVE@#To identify pathogenic variations of EXT1 and EXT2 genes in two Chinese pedigrees affected with hereditary multiple exostosis (HME).@*METHODS@#Genomic DNA was extracted from peripheral blood samples using a phenol-chloroform method. PCR and Sanger sequencing was conducted to amplify the exons and the flanking intronic regions of the EXT1 and EXT2 genes.@*RESULTS@#DNA sequencing has revealed a heterozygous missense variation c.812A>G (p.Tyr271Cys) in the exon 1 of EXT1 in pedigree 1, and a heterozygous frameshift variation c.1431dup (p.Ser478Leufs*43) in the exon 6 of EXT1 in the proband from pedigree 2. Both variations have co-segregated with the disease phenotype, which was also consistent with previous report.@*CONCLUSION@#Two heterozygous pathogenic variations underlying HME have been identified. The result has facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.


Subject(s)
Asian Continental Ancestry Group , Base Sequence , DNA Mutational Analysis , Exostoses, Multiple Hereditary , Genetics , Pathology , Frameshift Mutation , Humans , Mutation, Missense , N-Acetylglucosaminyltransferases , Genetics , Pedigree
11.
Article in Chinese | WPRIM | ID: wpr-776794

ABSTRACT

OBJECTIVE@#To explore the clinical features and mutations of the TRPM6 gene in an infant featuring hypomagnesemia and secondary hypocalcemia.@*METHODS@#Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Targeted exome sequencing was carried out to screen the potential mutations. Suspected mutations were verified by Sanger sequencing.@*RESULTS@#A novel homozygous c.5538delA (p.Q1846Qfs*2) mutation in the TRPM6 gene was identified in the proband, for which both of her parents were heterozygous carriers.@*CONCLUSION@#The homozygous frameshift mutation of TRPM6 gene (c.5538delA) probably underlies the disease in the proband. The finding has expanded the mutation spectrum of TRPM6 gene.


Subject(s)
DNA Mutational Analysis , Female , Frameshift Mutation , Humans , Hypocalcemia , Genetics , Infant , Magnesium Deficiency , Genetics , TRPM Cation Channels , Genetics
12.
Article in Chinese | WPRIM | ID: wpr-776760

ABSTRACT

OBJECTIVE@#To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome.@*METHODS@#Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing.@*RESULTS@#A heterozygous frameshift variation c.1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents.@*CONCLUSION@#The novel c.1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.


Subject(s)
DNA-Binding Proteins , Genetics , Female , Fingers , Congenital Abnormalities , Frameshift Mutation , Hair Diseases , Genetics , Humans , Langer-Giedion Syndrome , Genetics , Nose , Congenital Abnormalities , Pedigree , Transcription Factors , Genetics
13.
Article in Chinese | WPRIM | ID: wpr-776753

ABSTRACT

OBJECTIVE@#To identify pathogenic mutation of TSC1 and TSC2 genes in a patient with long-time misdiagnosis of epilepsy.@*METHODS@#Peripheral blood samples and clinical data of the patient and her 2 parents were collected. Potential mutation of TSC1 and TSC2 genes were detected by direct sequencing.@*RESULTS@#The patient had frequent episodes of epilepsy in addition with Shagreen patches for 10 years. A frame-shifting mutation c.2509_2512delAACA was detected in exon 20 of the TSC1 gene. This same mutation was not found in her unaffected parents.@*CONCLUSION@#The recurrent frame-shifting mutation c.2509_2512delAACA (p.Asn837ValfsX11) of the TSC1 gene probably underlies the disease in this patient.


Subject(s)
Diagnostic Errors , Epilepsy , Diagnosis , Genetics , Female , Frameshift Mutation , Humans , Tuberous Sclerosis , Diagnosis , Genetics , Tuberous Sclerosis Complex 1 Protein , Genetics , Tuberous Sclerosis Complex 2 Protein , Genetics
14.
Article in English | WPRIM | ID: wpr-719420

ABSTRACT

PURPOSE: Germline mutations within melanoma susceptibility genes are present only in minority of melanoma patients and it is expected that additional genes will be discovered with next generation sequence technology and whole-exome sequencing (WES). MATERIALS AND METHODS: Herein we performed WES on a cohort of 96 unrelated Polish patients with melanoma diagnosed under the age of 40 years who all screened negative for the presence of CDKN2A variants. A replication study using a set of 1,200 melanoma patient DNA samples and similarly large series of healthy controls was undertaken. RESULTS: We selected 21 potentially deleterious variants in 20 genes (VRK1, MYCT1, DNAH14, CASC3, MS4A12, PRC1, WWOX, CARD6, EXO5, CASC3, CASP8AP2, STK33, SAMD11, CNDP2, CPNE1, EFCAB6, CABLES1, LEKR1, NUDT17, and RRP15), which were identified by WES and confirmed by Sanger sequencing for an association study. Evaluation of the allele distribution among carriers and their relatives in available family trios revealed that these variants were unlikely to account for many familial cases of melanoma. Replication study revealed no statistically significant differences between cases and controls. CONCLUSION: Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5, and STK33 with melanoma risk.


Subject(s)
Alleles , Cohort Studies , DNA , Exome , Frameshift Mutation , Germ-Line Mutation , Humans , Incidence , Melanoma , Poland
15.
Article in English | WPRIM | ID: wpr-739231

ABSTRACT

OBJECTIVES: To investigate the genetic causes of hearing loss with enlarged vestibular aqueduct (EVA) in two children from unrelated two Chinese families. METHODS: Sanger sequencing of all coding exons in SLC26A4 (encoding Pendrin protein) was performed on the two patients, their sibling and parents respectively. To predict and visualize the potential functional outcome of the novel variant, model building, structure analysis, and in silico analysis were further conducted. RESULTS: The results showed that the proband from family I harbored a compound heterozygote of SLC26A4 c.1174A>T (p.N392Y) mutation and c.1181delTCT (p.F394del) variant in exon 10, potentially altering Pendrin protein structure. In family II, the proband was identified in compound heterozygosity with a known mutation of c.919-2A>G in the splice site of intron 7 and a novel mutation of c.1023insC in exon 9, which results in a frameshift and translational termination, consequently leading to truncated Pendrin protein. Sequence homology analysis indicated that all the mutations localized at high conservation sites, which emphasized the significance of these mutations on Pendrin spatial organization and function. CONCLUSION: In summary, this study revealed two compound heterozygous mutations (c.1174A>T/c.1181delTCT; c.919- 2A>G/c.1023insC) in Pendrin protein, which might account for the deafness of the two probands clinically diagnosed with EVA. Thus this study contributes to improve understanding of the causes of hearing loss associated with EVA and develop a more scientific screening strategy for deafness.


Subject(s)
Asian Continental Ancestry Group , Child , Clinical Coding , Computer Simulation , Deafness , Exons , Extravehicular Activity , Frameshift Mutation , Hearing Loss , Heterozygote , Humans , Introns , Mass Screening , Parents , Sequence Homology , Siblings , Vestibular Aqueduct
16.
Article in English | WPRIM | ID: wpr-719108

ABSTRACT

X-linked dominant mutations in lysosome-associated membrane protein 2 (LAMP2) gene have been shown to be the cause of Danon disease, which is a rare disease associated with clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. Cardiac involvement is a common manifestation and is the leading cause of death in Danon disease. We report a case of a 24-month-old boy with hemizygous LAMP2 mutation who presented with failure to thrive and early-onset hypertrophic cardiomyopathy. We applied targeted exome sequencing and found a novel hemizygous c.692del variant in exon 5 of the LAMP2 gene, resulting a frameshift mutation p.Thr231Ilefs*11. Our study indicates that target next-generation sequencing can be used as a fast and highly sensitive screening method for inherited cardiomyopathy.


Subject(s)
Cardiomyopathies , Cardiomyopathy, Hypertrophic , Cause of Death , Child, Preschool , Exome , Exons , Failure to Thrive , Frameshift Mutation , Glycogen Storage Disease Type IIb , Humans , Intellectual Disability , Lysosomal-Associated Membrane Protein 2 , Male , Mass Screening , Membrane Proteins , Methods , Muscular Diseases , Rare Diseases
17.
Article in English | WPRIM | ID: wpr-719106

ABSTRACT

Tricho-rhino-phalangeal syndrome (TRPS) is a hereditary disorder characterized by craniofacial and skeletal abnormalities. A mutation of the TRPS1 gene leads to TRPS type I or type III. A 20-year-old male patient visited our neurologic department with chronic fatigue. He presented with short stature, sparse hair, pear-shaped nose, and brachydactyly. Radiologic study showed short metacarpals, metatarsals with cone-shaped epiphyses, hypoplastic femur and hip joint. Panel sequencing for OMIM (Online Mendelian Inheritance in Man) listed genes revealed a de novo heterozygous frameshift mutation of c.1801_1802delGA (p.Arg601Lysfs*3) of exon 4 of the TRPS1 gene. The diagnosis of TRPS can be challenging due to the rarity and variable phenotype of the disease, clinicians should be aware of its characteristic clinical features that will lead a higher rate of diagnosis.


Subject(s)
Brachydactyly , Databases, Genetic , Diagnosis , Epiphyses , Exons , Fatigue , Femur , Frameshift Mutation , Hair , Hip Joint , Humans , Male , Metacarpal Bones , Metatarsal Bones , Nose , Phenotype , Wills , Young Adult
18.
Article in English | WPRIM | ID: wpr-715017

ABSTRACT

BACKGROUND: Mutations in ATP7B cause Wilson disease (WD). However, direct DNA full sequencing cannot detect all mutations in patients with WD. Multiplex ligation-dependent probe amplification (MLPA) analysis is reportedly useful in increasing the diagnostic yield in other genetic disorders with large deletions or insertions. The aim of this study was to evaluate whether the detection rate of ATP7B mutations can be increased by using MLPA. METHODS: We enrolled 114 children with WD from 104 unrelated families based on biochemical tests and direct DNA full sequencing. The patients with one or zero mutant allele were investigated using MLPA. We analyzed phenotypic correlations. RESULTS: Total allele frequency by full sequencing was 87.5%. Full sequencing revealed two mutant alleles in 80 of 104 unrelated children. One mutant allele was detected in 22 children, and no mutations were found in two children. Novel mutations including small deletions with frameshift mutations were identified by DNA sequencing. MLPA revealed no gross deletion or duplication in 24 children with one or zero mutant alleles. The number of detected mutations was not associated with hepatic manifestation, age of onset, Kayser-Fleischer ring, ceruloplasmin, and urinary Cu concentrations. CONCLUSION: MLPA showed a limited role to increase the mutation detection rate in children who do not receive a definite genetic diagnosis of WD through DNA full sequencing. This finding suggests that large deletions or duplications might be extremely rare in WD. Further development is needed to improve the genetic diagnosis of WD.


Subject(s)
Age of Onset , Alleles , Ceruloplasmin , Child , Diagnosis , DNA , Frameshift Mutation , Gene Frequency , Hepatolenticular Degeneration , Humans , Multiplex Polymerase Chain Reaction , Phenotype , Sequence Analysis , Sequence Analysis, DNA
19.
Article in English | WPRIM | ID: wpr-72416

ABSTRACT

Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 µmol/L; reference range, 11.2-48.2 µmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 µmol/L; reference range, 131-710 µmol/L) and glutamine (5,777 µmol/L; reference range, 376-709 µmol/L), whereas that of citrulline was decreased (2 µmol/L; reference range, 10-45 µmol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.


Subject(s)
Base Sequence , Carbamoyl-Phosphate Synthase (Ammonia)/chemistry , Carbamoyl-Phosphate Synthase I Deficiency Disease/diagnosis , Codon, Nonsense , Exons , Female , Frameshift Mutation , High-Throughput Nucleotide Sequencing , Humans , Infant, Newborn , Republic of Korea , Sequence Analysis, DNA , Urea Cycle Disorders, Inborn/diagnosis
20.
Genomics & Informatics ; : 48-50, 2017.
Article in English | WPRIM | ID: wpr-69979

ABSTRACT

Tumor tissues from biopsies or surgery are major sources for the next generation sequencing (NGS) study, but these procedures are invasive and have limitation to overcome intratumor heterogeneity. Recent studies have shown that driver alterations in tumor tissues can be detected by liquid biopsy which is a less invasive technique capable of both capturing the tumor heterogeneity and overcoming the difficulty in tissue sampling. However, it is still unclear whether the driver alterations in liquid biopsy can be detected by targeted NGS and how those related to the tissue biopsy. In this study, we performed whole-exome sequencing for a breast cancer tissue and identified PTEN p.H259fs*7 frameshift mutation. In the plasma DNA (liquid biopsy) analysis by targeted NGS, the same variant initially identified in the tumor tissue was also detected with low variant allele frequency. This mutation was subsequently validated by digital polymerase chain reaction in liquid biopsy. Our result confirm that driver alterations identified in the tumor tissue were detected in liquid biopsy by targeted NGS as well, and suggest that a higher depth of sequencing coverage is needed for detection of genomic alterations in a liquid biopsy.


Subject(s)
Biopsy , Breast Neoplasms , Breast , DNA , Frameshift Mutation , Gene Frequency , Plasma , Polymerase Chain Reaction , Population Characteristics
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