OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*

OBJECTIVETo identify the pathogenic mutation underlying piebaldism in a Chinese family.

METHODSA three-generation family showing an autosomal dominant transmission of piebaldism was recruited. Potential mutations of the KIT and SNAI2 genes were detected by PCR-amplification of the exons and exon-intron boundaries and direct sequencing.

RESULTSA heterozygous missense mutation, c.2585T>C, was identified in exon 18 of the KIT gene. The mutation, together with a c.2586G>C polymorphism, has led to substitution of Leucine by Proline at amino acid residue 862 (p.Leu862Pro) of the mast/stem cell growth factor receptor KIT. The same mutation was detected in all affected family members but not in dbSNP142, the 1000 Genomes draft database, or the Human Gene Mutation Database. No mutation of the SNAI2 gene was found.

CONCLUSIONThe c.2585T>C (p.Leu862Pro) mutation in the KIT gene probably underlies the piebaldism phenotype in this family.

Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; methods ; Exons ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Heterozygote ; Humans ; Infant ; Introns ; genetics ; Male ; Mutation, Missense ; Pedigree ; Phenotype ; Piebaldism ; ethnology ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-kit ; genetics ; Sequence Homology, Amino Acid

No abstract available.
Base Sequence ; Bone Marrow/pathology ; DNA Mutational Analysis ; Exons ; Female ; Humans ; Immunophenotyping ; Leukemia, Mast-Cell/*diagnosis/genetics ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; Proto-Oncogene Proteins c-kit/*genetics

No abstract available.
Acanthosis Nigricans/diagnosis/*etiology ; Biopsy ; Gastrointestinal Stromal Tumors/chemistry/*complications/pathology ; Humans ; Immunohistochemistry ; Laparoscopy ; Male ; Middle Aged ; Paraneoplastic Syndromes/diagnosis/*etiology ; Peritoneal Neoplasms/chemistry/*complications/pathology ; Proto-Oncogene Proteins c-kit/analysis ; Tomography, X-Ray Computed ; Tumor Markers, Biological/analysis

This study was aimed to investigate the c-kit mutation in acute myeloid leukemia (AML) patients with AML1-ETO and analyze its relation with clinical and laboratorial features and prognosis. PCR and sequencing methods were used to detect the c-kit 17 exon mutations in 31 AML patients with AML1-ETO. The relation of the c-kit mutation with clinical features, results of laboratorial examination and prognosis of disease were analyzed. The results showed that the c-kit mutation was found in 14 out of 31 AML patients and the mutation frequency was 45.16%. Male patients had a higher incidence of c-kit mutation than that of female patients (P = 0.020). The proportion of patients with newly diagnosed white blood cell>10×10(9)/L and with extramedullary infiltration in mutated group were higher than those in unmutated group respectively. No significant difference was observed at the age (P = 0.437) and the rate of bone marrow blasts(P = 0.510) between the above mentioned two groups. The difference in complete remission rate (64.29% vs 80%, P = 0.344)and relapse rate (58.33% vs 21.43%, P = 0.054) between c-kit mutated and c-kit unmutated groups were not significant. While the c-kit mutated group had a significant higher death rate as compared with c-kit unmutated group (57.14% vs 20%, P = 0.039). It is concluded that the c-kit mutation is frequent in AML patients with AML1-ETO and the c-kit mutated patients have a poor prognosis. It is important to detect c-kit mutation in routine clinical practice for patient's risk stratification, evaluation of prognosis and selection of effective treatment.
Adolescent ; Adult ; Aged ; Core Binding Factor Alpha 2 Subunit ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; Male ; Middle Aged ; Mutation ; Oncogene Proteins, Fusion ; genetics ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; RUNX1 Translocation Partner 1 Protein ; Treatment Outcome ; Young Adult

This study was aimed to explore whether multiple common gene mutations of leukemia synergistically involved in acute promyelocytic leukemia (APL) pathogenesis, and to investigate their relevance to clinical features, cytogenetics and molecular risk stratification. 84 specimens of admitted de novo APL patients from February 2005 to October 2010 were collected, the gene mutations of bone marrow mononuclear cells and clinical features of mutation-positive patients were analyzed by genomic DNA-PCR. The results indicated that the prevalence of mutations was 60.7% (51/84), in which the mutations with the highest incidence were found as FLT3-ITD, reaching 27.4% (23/84). Next, there were 12 cases WT1 mutation, 9 for FLT3-TKD, 7 for TET2, 5 for N-RAS, 4 for ASXL1, 2 for EZH2 mutation and 1 positive case in MLL-PTD, IDH1 and CBL mutation respectively. No mutation was found in other JAK1, DNMT3, c-Kit, NPM1, IDH2, RUNX1 and JAK2 (V617F) common leukemia-related genes. Combined analysis with clinical data demonstrated that the patients with FLT3-ITD mutation displayed higher white blood cell counts, while the patients with N-RAS mutation showed lower platelet counts. Overall survival of these patients was obviously shorten as compared with patients with wild-type. This difference between mutant and wild-type of all above mentioned cases was statistically significant (P < 0.05). The difference between APL with simple t (15;17) and additional abnormal karyotype was not statistically significant. It is concluded that the FLT3-ITD mutation is recurrent genetic change in APL, and together with N-RAS mutation indicates poor prognosis. Additional abnormal karyotype does not associate with prognosis of APL.
Adolescent ; Adult ; Aged ; Child ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Enhancer of Zeste Homolog 2 Protein ; Female ; Genes, ras ; Humans ; Leukemia, Promyelocytic, Acute ; genetics ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Polycomb Repressive Complex 2 ; genetics ; Prognosis ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins c-kit ; genetics ; Repressor Proteins ; genetics ; Tandem Repeat Sequences ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo evaluate the prevalence and distribution of C-kit, NPM1 and FLT3 gene mutations in patients with acute myeloid leukemia (AML), and to analyze the relationship between the gene mutations and their prognosis.

METHODSMutations in exon 8 and 17 of C-kit gene, exon 12 of NPM1 gene, exon 20 of FLT3-TKD gene, and exon 14/15 of FLT3-ITD gene were detected by direct sequencing. Clinical data was collected and followed up if the patient had accepted treatment in our hospital.

RESULTSAmong the 656 AML patients, mutations in C-kit exon 8 were found in 6 patients (0.9%), C-kit exon 17 in 33 (5.0%), NPM1 in 169 (25.8%), FLT3-TKD in 46 (7.1%), and FLT3-ITD in 178 (27.1%). Six subtypes of mutations were detected in C-kit exon 8, 8 in C-kit exon 17, 11 in FLT3-TKD, 15 in NPM1, of which 5 were not reported before. C-kit exon 17 mutations were more frequently detected in patients with t(8;21) and exon 8 in patients with inv(16) cytogenetic abnormality. No other gene mutations except FLT3 were detected in M(3) patients. NPM1 and ITD mutations were often detected in individuals with normal cytogenetics or M(5) and M(1) of FAB classification, and accompanied with high white blood cell counts in peripheral blood, high blast counts in bone marrow and low CD34 expression. The older the patients were when diagnosed, the more gene mutations and the higher white blood cell count were detected. More mutations were found in individuals with normal karyotype than that with other karyotypes. It appeared that FLT3-ITD was significantly associated with shorter overall survival (OS) (P = 0.004), NPM1 was not significantly associated with OS, but NPM1(+)/ITD(-) patients had the longest OS.

CONCLUSIONSOur results showed that the mutation types and amounts had particular distribution in MICM subtypes, and were associated with white blood cell counts in peripheral blood, blast counts in bone marrow and prognosis. Especially for patients with normal karyotype, the genetic mutations could be new molecule marker.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; DNA Mutational Analysis ; Female ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo explore the relationship between c-kit and platelet-derived growth factor receptor alpha(PDGFRA) gene mutation features and the prognosis of gastrointestinal stromal tumor(GIST).

METHODSClinicopathological, genetic testing and follow-up informations of patients admitted to the Shanxi Tumor Hospital from June 2000 to January 2009 were collected. The survival was calculated and univariate analysis was conducted using the Kaplan-Meier method. Multivariate analysis was conducted by the Cox regression method.

RESULTSThe 5-year disease-free survival rate was 61.5% and the 5-year overall survival rate was 67.4%. The 5-year disease-free survival rates of patients without disease among those with c-kit exon 11 mutation (n=77), c-kit exon 9 mutation(n=4), and PDGFRA exon 18 mutation (n=2) were 63.4%, 14.3% and 100%, and the 5-year overall survival rates were 70.8%, 50.0% and 100%, respectively. In the patients with c-kit exon 11 mutation, the 5-year disease-free survival rates among those with point mutations(n=26), deletion mutations(n=44), and duplication mutations(n=7) were 87.1%, 44.9% and 80.0%, and the 5-year overall survival rates were 88.1%, 57.0% and 100%, respectively. There were significant differences in overall survival among different factors. Multivariate analysis showed that gene mutation was not the independent factor of prognosis(P=0.492).

CONCLUSIONSIn GIST patients undergoing surgery without imatinib treatment, mutated genotype is better than wild type in terms of prognosis. Gene mutation is not the independent factor of prognosis in GIST patients.

DNA Mutational Analysis ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; genetics ; surgery ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins c-kit ; genetics ; Receptor, Platelet-Derived Growth Factor alpha ; genetics

Combined hepatocellular carcinoma and cholangiocarcinoma (combined HCC-CC) is a rare subtype of primary liver cancer. We investigated the histopathologic features of transitional or intermediate areas in 21 combined HCC-CCs and immunophenotypes using different hepatic progenitor cell markers (CK7, CK19, c-kit, NCAM, and EpCAM). Major histologic findings of transitional or intermediate areas of 21 combined HCC-CCs included strands/trabeculae of small, uniform, oval-shaped cells with scant cytoplasm and hyperchromatic nuclei embedded within an abundant stroma, small cells with an antler-like anastomosing pattern, and solid nests of intermediate hepatocyte-like cells surrounded by small cells in periphery, in order of frequency. The intermediate area of one tumor was composed predominantly of spindle cells arranged in short fascicles. Immunophenotype of tumor cells with intermediate morphology suggested a progenitor cell origin for this tumor. Clinical findings of combined HCC-CC showed a closer resemblance with those of HCC than those of CC. In univariate analysis, tumor size, TNM stage, and serum alpha-fetoprotein levels showed a significant association with poor patient survival. Serum alpha-fetoprotein level was an independent prognostic indicator in multivariate analysis. In conclusion, an awareness of the clinicopathologic features, specifically the various morphologic features of intermediate areas in this tumor, is essential for prevention of potential misdiagnosis as another tumor.
Adult ; Aged ; Antigens, Neoplasm/metabolism ; Carcinoma, Hepatocellular/*pathology ; Cell Adhesion Molecules/metabolism ; Cholangiocarcinoma/*pathology ; Female ; Humans ; Immunophenotyping ; Keratin-19/metabolism ; Keratin-7/metabolism ; Liver Neoplasms/*pathology ; Male ; Middle Aged ; Neural Cell Adhesion Molecules/metabolism ; Prognosis ; Proto-Oncogene Proteins c-kit/metabolism ; alpha-Fetoproteins/analysis

OBJECTIVETo assess the prevalence of several tyrosine kinases (TKs) gene mutations including c-Kit, FLT3 and JAK2 V617F in core binding factor related acute myeloid leukemia (CBF-AML), and analyze their impact on clinical characteristics and prognosis.

METHODSMutations of c-Kit, FLT3-ITD and FLT3-TKD were detected by genomic DNA PCR and sequencing, and JAK2 V617F mutation screening by allele-specific PCR in 58 newly diagnosed CBF-AML patients [28 AML with inv(16) and 30 with t(8;21)], and analyze the patients clinical characteristics and prognoses.

RESULTSc-Kit aberrations were detected in 32.8% cases, including 6 cases mutated in exon 8 (mutKIT8) and 13 mutated in exon 17 (mutKIT17). MutKIT8 was more prominent in inv(16) than in t(8;21) patients (21.4% vs 0, P = 0.009). Only 2 cases had FLT3-ITD and 7 (12.1%) FLT3-TKD mutations. The result of JAK2 V617F mutation screenings in these CBF-AML patients was negative. The frequency of receptor tyrosine kinases(RTK) mutations was 46.6% and only one case had two kinds of missense mutations (mutKIT8 & TKD(+)). Median age of onset was higher for mutKIT17 than for wide-type c-Kit (wtKIT) patients (55 vs 31, P = 0.003). c-Kit mutations were significantly associated with decreased overall survival (OS) and continuous complete remission (CCR) rates (P = 0.053, and 0.048 respectively), and so did more for exon17 mutated patients reduced (P = 0.005, and 0.013 respectively). FLT3-TKD mutation showed no effects on prognosis of CBF-AML patients.

CONCLUSIONSRTK mutations are common in patients with CBF-AML. c-Kit mutations frequently and JAK2V617F mutation rarely appear in CBF-AML. c-Kit mutations, especially mutKIT17 confers higher relapse risk and poorer prognosis.

Adolescent ; Adult ; Aged ; Core Binding Factors ; DNA Mutational Analysis ; Female ; Humans ; Janus Kinase 2 ; genetics ; Leukemia, Myeloid, Acute ; diagnosis ; etiology ; genetics ; Male ; Middle Aged ; Mutation ; Prognosis ; Protein-Tyrosine Kinases ; genetics ; Proto-Oncogene Proteins c-kit ; genetics ; Young Adult ; fms-Like Tyrosine Kinase 3 ; genetics