8,257 results match your criteria kit mutations


A new sensitive and fast assay for the detection of EGFR mutations in liquid biopsies.

PLoS One 2021 24;16(6):e0253687. Epub 2021 Jun 24.

Institute of Pathology, Locarno, Switzerland.

Background: A major perspective for the use of circulating tumor DNA (ctDNA) in the clinical setting of non-small cell lung cancer (NSCLC) is expected as predictive factor for resistance and response to EGFR TKI therapy and, especially, as a non-invasive alternative to tissue biopsy. However, ctDNA is both highly fragmented and mostly low concentrated in plasma and serum. On this basis, it is important to use a platform characterized by high sensitivity and linear performance in the low concentration range. Read More

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Earlier extracranial progression and shorter survival in ALK-rearranged lung cancer with positive liquid rebiopsies.

Transl Lung Cancer Res 2021 May;10(5):2118-2131

Division of Cancer Genome Research, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Background: Liquid rebiopsies can detect resistance mutations to guide therapy of anaplastic lymphoma kinase-rearranged (ALK) non-small-cell lung cancer (NSCLC) failing tyrosine kinase inhibitors (TKI). Here, we analyze how their results relate to the anatomical pattern of disease progression and patient outcome.

Methods: Clinical, molecular, and radiologic characteristics of consecutive TKI-treated ALK NSCLC patients were analyzed using prospectively collected plasma samples and the 17-gene targeted AVENIO kit, which covers oncogenic drivers and all exons. Read More

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Case report of a clinically indolent but morphologically high-grade cutaneous mast cell tumor in an adult: atypical cutaneous mastocytoma or mast cell sarcoma?

J Cutan Pathol 2021 Jun 21. Epub 2021 Jun 21.

Pathology and Medical Biology department, University Medical Centre Groningen, Groningen, The Netherlands.

We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred within two years, was re-excised after four years and did not recur >six year after diagnosis. The tumor showed progressive cytonuclear atypia and a high mitotic and proliferation rate by Ki67-staining from the onset. Read More

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Exon-1 skipping and intron-1 retaining by alternative splicing of the c-KIT gene encodes a novel splice variant in the skin of Merino sheep (Ovis aries).

Mol Biol Rep 2021 Jun 20. Epub 2021 Jun 20.

School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy.

c-KIT, a type III receptor protein tyrosine kinase, plays an essential role in melanocyte development, migration, and survival. Mutations within the c-KIT gene are previously shown to cause the white coat color phenotypes in pigs, mice, goats, and humans. However, up so far, the splicing isoform(s), genomic architecture of c-KIT have not been characterized well in merino sheep. Read More

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A Rare Case of Intestinal Ulcer.

Gastroenterology 2021 Jun 16. Epub 2021 Jun 16.

Department of Gastroenterology, Daping Hospital, Army Medical University of PLA, Chongqing, China. Electronic address:

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Proliferation of SARS-CoV-2 B.1.1.7 Variant in Pakistan-A Short Surveillance Account.

Front Public Health 2021;9:683378. Epub 2021 May 31.

Department of Virology, National Institute of Health, Islamabad, Pakistan.

The emergence of a more transmissible variant of SARS-CoV-2 (B1. 1.7) in the United Kingdom (UK) during late 2020 has raised major public health concerns. Read More

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Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type.

Oncotarget 2021 Jun 8;12(12):1178-1186. Epub 2021 Jun 8.

Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA, USA.

Further characterization of thymic epithelial tumors (TETs) is needed. Genomic information from 102 evaluable TETs from The Cancer Genome Atlas (TCGA) dataset and from the IU-TAB-1 cell line (type AB thymoma) underwent clustering analysis to identify molecular subtypes of TETs. Six novel molecular subtypes (TH1-TH6) of TETs from the TCGA were identified, and there was no association with WHO histologic subtype. Read More

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Rapid and simultaneous identification of three mutations by the Novaplex™ SARS-CoV-2 variants I assay kit.

J Clin Virol 2021 May 29;141:104877. Epub 2021 May 29.

Department of Infectious, Respiratory and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus. 207 Uehara, Nishihara, Okinawa 903-0215, Japan.

Background: . The emergence of SARS-CoV-2 variants has caused an unexpected rebound globally. The World Health Organization has listed three variants (B. Read More

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The role of alteration and 4q12 amplification in IDH-WT glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab050. Epub 2021 Mar 31.

Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.

Background: Recent studies have identified that glioblastoma IDH-wildtype (GBM IDH-WT) might be comprised of molecular subgroups with distinct prognoses. Therefore, we investigated the correlation between genetic alterations and survival in 282 GBM IDH-WT patients, to identify subgroups with distinct outcomes.

Methods: We reviewed characteristics of GBM IDH-WT (2009-2019) patients analyzed by next-generation sequencing interrogating 205 genes and 26 rearrangements. Read More

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Vulvar Melanoma: Molecular Characteristics, Diagnosis, Surgical Management, and Medical Treatment.

Am J Clin Dermatol 2021 Jun 14. Epub 2021 Jun 14.

Department of Dermatology and Allergology, Paracelsus Medical University, Salzburg, Austria.

Ten percent of all women have pigmented vulvar lesions. Fortunately, most of these are benign but 1% of all melanomas in women affect the vulva. While the mortality rate of cutaneous melanoma has dropped by 7% annually during the last 5 years, the prognosis of vulvar melanoma remains dismal: the 5-year overall survival rate is 47% compared with 92% for cutaneous melanoma. Read More

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Mutations of the and gene in gastrointestinal stromal tumors among hakka population of Southern China.

Niger J Clin Pract 2021 Jun;24(6):814-820

Center for Precision Medicine; Guangdong Provincial Key Laboratory of Precision Medicine, Clinical and Translational Research in Hakka Population, Meizhou People's Hospital; Guangdong Provincial Engineering and Technology Research Center for Clinical Molecular Diagnostics and Antibody Therapeutics, No. 63 Huangtang Road, Meijiang District, Meizhou, PR China.

Aims: The aim of the present study was to investigate mutation status of the cKit and PDGFRA genes in patients with a gastrointestinal stromal tumor (GIST).

Methods: In total, 96 patients with a GIST were included in the study, in which polymerase chain reaction amplification and gene sequencing were used to detect the sequences of exons 9, 11, 12, 13, 14, 17, and 18 in KIT and exons 12, 14, and 18 in PDGFRA.

Results: KIT mutations were detected in 65 cases (67. Read More

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Droplet digital polymerase chain reaction assay for the detection of the minor clone of KIT D816V in paediatric acute myeloid leukaemia especially showing RUNX1-RUNX1T1 transcripts.

Br J Haematol 2021 Jun 13. Epub 2021 Jun 13.

Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

KIT D816V mutation within exon 17 has been particularly reported as one of the poor prognostic factors in pediatric acute myeloid leukemia (AML) with RUNX1-RUNX1T1. The exact frequency and the prognostic impact of KIT D816V minor clones at diagnosis were not examined. In this study, the minor clones were examined and the prognostic significance of KIT D816V mutation in pediatric patients was investigated. Read More

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Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance.

Nat Commun 2021 06 11;12(1):3579. Epub 2021 Jun 11.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. Read More

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A new GNPAT variant of foetal rhizomelic chondrodysplasia punctata.

Mol Genet Genomic Med 2021 Jun 10:e1733. Epub 2021 Jun 10.

Division of Prenatal Diagnosis, Meyer Children's Hospital, Florence, Italy.

Background: Rhizomelic chondrodysplasia punctata (RCDP) is a clinical entity resulting from defects of peroxisomal metabolism whose clinical phenotype is characterized by rhizomelia, calcified foci in periarticular cartilage, coronal lesions of vertebral bodies, cataracts and severe cognitive delay. Usually, survival does not exceed the first decade of life. Transmission is autosomal recessive and is related to mutations in the PEX7, GNPAT or AGPS. Read More

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Efficacy of RyR2 inhibitor EL20 in induced pluripotent stem cell-derived cardiomyocytes from a patient with catecholaminergic polymorphic ventricular tachycardia.

J Cell Mol Med 2021 Jun 10. Epub 2021 Jun 10.

Department of Molecular Physiology & Biophysics, Cardiovascular Research Institute, Baylor College of Medicine, Houston, TX, USA.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia syndrome that often leads to sudden cardiac death. The most common form of CPVT is caused by autosomal-dominant variants in the cardiac ryanodine receptor type-2 (RYR2) gene. Mutations in RYR2 promote calcium (Ca ) leak from the sarcoplasmic reticulum (SR), triggering lethal arrhythmias. Read More

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Targeting Mutated p53 Dependency in Triple-Negative Breast Cancer Cells Through CDK7 Inhibition.

Front Oncol 2021 24;11:664848. Epub 2021 May 24.

Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.

Background: Cyclin-dependent kinase 7 (CDK7) is crucial for cell cycle progression and gene expression transcriptional regulation, which are often not assessed in cancer developing process. CDK7 inhibitors have emerged as promising drugs for treating diverse cancers, including breast cancer. However, the mechanism behind its anticancer effect has not been well investigated. Read More

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TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4.

Nat Commun 2021 06 9;12(1):3481. Epub 2021 Jun 9.

Institute of Translational Medicine, Zhejiang University City College, Hangzhou, P. R. China.

TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Read More

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Recurrent KRAS, KIT and SF3B1 mutations in melanoma of the female genital tract.

BMC Cancer 2021 Jun 8;21(1):677. Epub 2021 Jun 8.

Department of Pathology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, No 420, Fuma Road, Fuzhou, 350014, Fujian Province, China.

Background: Malignant melanoma of the female genital tract is relatively uncommon and accounts for 3-7% of all melanoma localizations. This study aimed to identify driver genes in melanoma of the female genital tract with the purpose of enhancing understanding of disease pathogenesis and identifying potential new therapeutic targets to develop effective therapies.

Methods: KIT (CD117) and BRAF expression were detected immunohistochemically. Read More

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Longitudinal genotype-phenotype analysis in 86 PAX6-related aniridia patients.

JCI Insight 2021 Jun 8. Epub 2021 Jun 8.

Department of Development, Ageing and Disease, UCL Institute of Ophthalmology, London, United Kingdom.

Aniridia is most commonly caused by haploinsufficiency of the PAX6 gene, characterised by variable iris and foveal hypoplasia, nystagmus, cataracts, glaucoma and aniridia related keratopathy (ARK). Genotype-phenotype correlations have previously been described, however detailed longitudinal studies of aniridia are less commonly reported. We identified eighty-six patients from sixty-two unrelated families with molecularly confirmed heterozygous PAX6 variants from a United Kingdom (UK)-based single-centre ocular genetics service. Read More

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REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer.

BMC Cancer 2021 Jun 7;21(1):674. Epub 2021 Jun 7.

Department of Colorectal Surgery, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, Japan.

Background: Previous clinical trials have demonstrated the potential efficacy of rechallenge with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer (mCRC). Moreover, post hoc biomarker analyses of clinical trials has suggested that RAS status in circulating tumor DNA (ctDNA) has a high probability to select patients who could benefit from anti-EGFR mAb rechallenge.

Methods: This trial is composed of 2 phases: a monitoring phase (REMARRY) and a trial phase (PURSUIT). Read More

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Melanoma genomics: a state-of-the-art review of practical clinical applications.

Br J Dermatol 2021 Jun 6. Epub 2021 Jun 6.

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School Boston, MA, 02114, USA.

Our collective understanding of melanoma genomics has rapidly expanded in the past decade, bringing great promise to patients affected with the most severe and aggressive cases of melanoma. In this review, we present the practical clinical impact of genetics and genomics on modern melanoma diagnosis and treatment. Characterization of somatic driver mutations, which can be used to distinguish different subtypes of melanoma such as nonacral cutaneous melanoma (NACM), desmoplastic melanoma (DM), acral melanoma (AM), mucosal melanoma (MM) and uveal melanoma (UM), has led to the development of many targeted therapies against these tumours. Read More

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KIT Mutation in Gastric Gastrointestinal Stromal Tumor in a Patient With Familial Paraganglioma Syndrome Type 4.

AACE Clin Case Rep 2021 May-Jun;7(3):174-176. Epub 2021 Jan 7.

Department of Medicine, Queen's University, Kingston, Ontario, Canada.

Objective: Familial paraganglioma syndrome type 4 is associated with mutations in the succinate dehydrogenase complex subunit B (SDHB) gene. We report the case of a patient with familial paraganglioma syndrome type 4 with the mutation c.600G>T; p. Read More

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January 2021

Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia.

Front Oncol 2021 20;11:677833. Epub 2021 May 20.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Centre for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two cycles of consolidation (n = 421). The latter time point was proved as a superior indicator with independent prognostic significance for both relapse-free survival (RFS, HR = 3. Read More

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Starting Imatinib at 400 mg Daily in Patients with Gastrointestinal Stromal Tumors Harboring KIT Exon 9 Mutations: A Retrospective, Multicenter Study.

Target Oncol 2021 Jun 5. Epub 2021 Jun 5.

Department of Cancer Medicine, Gustave Roussy, Villejuif, France.

Background: Retrospective analyses suggest that patients with advanced KIT exon 9-mutated gastrointestinal stromal tumors (GISTs) receiving imatinib 800 mg (rather than 400 mg) daily have better outcomes. In the adjuvant setting, the question of the optimal dose of imatinib remains unsettled.

Objective: We aimed to retrospectively assess the activity of imatinib 400 mg in both the adjuvant and the advanced settings. Read More

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Generation of six human iPSC lines from patients with a familial Alzheimer's disease (n = 3) and sex- and age-matched healthy controls (n = 3).

Stem Cell Res 2021 May 30;53:102379. Epub 2021 Apr 30.

Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; International Clinical Research Center (ICRC), St. Anne's University Hospital, Brno, Czech Republic. Electronic address:

Human induced pluripotent stem cell (iPSC) lines were generated from primary human fibroblasts isolated from three patients with a familial form of Alzheimer's disease (AD) and three healthy control individuals. Two AD-iPSC lines carry a PSEN1 mutation A246E; the third cell line carries a PSEN2 mutation N141I. The fibroblasts were reprogrammed with Yamanaka factors (OSKM) using a commercially available Epi5 Reprogramming Kit. Read More

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Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours.

BMJ Open 2021 06 3;11(6):e044543. Epub 2021 Jun 3.

Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Cancer Hospital Chinese Academy of Medical Sciences, Chaoyang District, Beijing, China

Introduction: Limited clinical studies have been conducted on rare solid tumours, and there are few guidelines on the diagnosis and treatment, including experiences with targeted therapy and immunotherapy, of rare solid tumours in China, resulting in limited treatment options and poor outcomes. This study first proposes a definition of rare tumours and is designed to test the preliminary efficacy of targeted and immunotherapy drugs for the treatment of rare tumours.

Methods And Analysis: This is a phase II, open-label, non-randomised, multiarm, single-centre clinical trial in patients with advanced rare solid tumours who failed standard treatment; the study aims to evaluate the safety and efficacy of targeted drugs in patients with advanced rare solid tumours with corresponding actionable alterations, as well as the safety and efficacy of immune checkpoint (programmed death receptor inhibitor 1, PD-1) inhibitors in patients with advanced rare solid tumours without actionable alterations. Read More

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Heterodimer formation with retinoic acid receptor RXRα modulates coactivator recruitment by peroxisome proliferator-activated receptor PPARγ.

J Biol Chem 2021 May 31:100814. Epub 2021 May 31.

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, D-60596 Frankfurt, Germany. Electronic address:

Nuclear receptors (NRs) activate transcription of target genes in response to binding of ligands to their ligand binding domains (LBDs). Typically, in vitro assays use either gene expression or the recruitment of coactivators to the isolated LBD of the NR of interest to measure NR activation. However, this approach ignores that NRs function as homo- as well as heterodimers, and that the LBD harbors the main dimerization interface. Read More

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Gata2-L359V impairs primitive and definitive hematopoiesis and blocks cell differentiation in murine chronic myelogenous leukemia model.

Cell Death Dis 2021 Jun 2;12(6):568. Epub 2021 Jun 2.

Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine, Ruijin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, Shanghai, China.

GATA2, a key transcription factor in hematopoiesis, is frequently mutated in hematopoietic malignancies. How the GATA2 mutants contribute to hematopoiesis and malignant transformation remains largely unexplored. Here, we report that Gata2-L359V mutation impeded hematopoietic differentiation in murine embryonic and adult hematopoiesis and blocked murine chronic myeloid leukemia (CML) cell differentiation. Read More

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Who's Driving? Switch of Drivers in Immunotherapy-Treated Progressing Sinonasal Melanoma.

Cancers (Basel) 2021 May 31;13(11). Epub 2021 May 31.

Department of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.

Mucosal melanoma can be driven by various driver mutations in genes such as , , or . However, some cases present with only weak drivers, or lacking known oncogenic drivers, suggesting immunotherapy over targeted therapy. While resistance mechanisms to immunotherapy in cutaneous melanoma have been uncovered, including alterations in /, or , a switch of oncogenic drivers under immunotherapy has not yet been observed. Read More

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