6,634 results match your criteria distinct mutational

Targeted Mutational Analysis of Cortisol-Producing Adenomas.

J Clin Endocrinol Metab 2021 Sep 17. Epub 2021 Sep 17.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Background: Somatic gene mutations have been identified in only about half of cortisol-producing adenomas (CPA). Affected genes include PRKACA, GNAS, PRKAR1A, and CTNNB1.

Objective: To expand our understanding of the prevalence of somatic mutations in CPA from patients with overt Cushing syndrome (OCS) and "subclinical" mild autonomous cortisol excess (MACE), with an immunohistochemistry (IHC)‒guided targeted amplicon sequencing approach using formalin-fixed paraffin-embedded (FFPE) tissue. Read More

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September 2021

SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence.

Prostate 2021 Sep 17. Epub 2021 Sep 17.

Departament of Health and Experimental Sciences, Universitat Pompeu Fabra, Barcelona, Spain.

Background: In the non-ETS fusion of prostate cancer (PCa) pathway, SPOP mutations emerge as a distinct oncogenic driver subclass. Both SPOP downregulation and mutation can lead to SPOP target stabilization promoting dysregulation of key regulatory pathways. CHD1 gene is commonly deleted in PCa. Read More

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September 2021

RetS inhibits Pseudomonas aeruginosa biofilm formation by disrupting the canonical histidine kinase dimerization interface of GacS.

J Biol Chem 2021 Sep 13:101193. Epub 2021 Sep 13.

Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. Electronic address:

Bacterial signaling histidine kinases (HKs) have long been postulated to function exclusively through linear signal transduction chains. However, several HKs have recently been shown to form complex multikinase networks (MKNs). The most prominent MKN, involving the enzymes RetS and GacS, controls the switch between the motile and biofilm lifestyles in the pathogenic bacterium Pseudomonas aeruginosa. Read More

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September 2021

Structure-based classification predicts drug response in EGFR-mutant NSCLC.

Nature 2021 Sep 15. Epub 2021 Sep 15.

Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA.

Epidermal growth factor receptor (EGFR) mutations typically occur in exons 18-21 and are established driver mutations in non-small cell lung cancer (NSCLC). Targeted therapies are approved for patients with 'classical' mutations and a small number of other mutations. However, effective therapies have not been identified for additional EGFR mutations. Read More

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September 2021

Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases.

Mod Pathol 2021 Sep 14. Epub 2021 Sep 14.

Department of Pathology, University of Toronto, Toronto, ON, Canada.

A distinct renal tumor has recently been described as "high-grade oncocytic renal tumor" and "sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm". The Genitourinary Pathology Society (GUPS) consensus proposed a unifying name "eosinophilic vacuolated tumor" (EVT) for this emerging entity. In this multi-institutional study, we evaluated 19 EVTs, particularly their molecular features and mutation profile, using next-generation sequencing. Read More

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September 2021

Characterization of KRAS Mutation Subtypes in Non-Small Cell Lung Cancer.

Mol Cancer Ther 2021 Sep 13. Epub 2021 Sep 13.

medical oncology, Fox Chase Cancer Center

KRAS is the most commonly mutated oncogene in NSCLC and development of direct KRAS inhibitors has renewed interest in this molecular variant. Different KRAS mutations may represent a unique biologic context with different prognostic and therapeutic impact. We sought to characterize genomic landscapes of advanced, KRAS mutated NSCLC in a large national cohort to help guide future therapeutic development. Read More

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September 2021

Clinical and Molecular Characterizations of Papillary Thyroid Cancer in Children and Young Adults: a Multicenter Retrospective Study.

Thyroid 2021 Sep 13. Epub 2021 Sep 13.

Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, 71140, Department of Head and Neck Surgery, Shanghai, China;

Background Papillary thyroid carcinoma (PTC) is a rare malignancy in children and young adults (CAYA). It often presents with aggressive disease patterns and advanced stages, which are clinically distinct from those in adult patients. Here, we sought to characterize and better understand the clinical variants of PTC in CAYA and explore the underlying mechanisms. Read More

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September 2021

Characterization of immune landscape in papillary thyroid cancer reveals distinct tumor immunogenicity and implications for immunotherapy.

Oncoimmunology 2021 7;10(1):e1964189. Epub 2021 Sep 7.

Department of Radiation Oncology, University Hospital, LMU Munich, Germany.

Although the vast majority of patients with papillary thyroid cancer (PTC) have a favorable prognosis when conventional treatments are implemented, local recurrence and distant metastasis of advanced PTCs still hamper the survival and clinical management in certain patients. As immune checkpoint blockade (ICB) therapy achieves a great success in some advanced cancers, we aimed to investigate the immune landscape in PTC and its potential implications for prognosis and immunotherapy. In this study, different algorithms were conducted to estimate immune infiltration in PTC samples. Read More

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September 2021

Comprehensively Exploring the Mutational Landscape and Patterns of Genomic Evolution in Hypermutated Cancers.

Cancers (Basel) 2021 Aug 26;13(17). Epub 2021 Aug 26.

Department of Pharmacology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.

Tumor heterogeneity results in more than 50% of hypermutated cancers failing to respond to standard immunotherapy. There are numerous challenges in terms of drug resistance, therapeutic strategies, and biomarkers in immunotherapy. In this study, we analyzed primary tumor samples from 533 cancer patients with six different cancer types using deep targeted sequencing and gene expression data from 78 colorectal cancer patients, whereby driver mutations, mutational signatures, tumor-associated neoantigens, and molecular cancer evolution were investigated. Read More

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Phenogenomic characterization of a newly domesticated and novel species from the genus .

Appl Environ Microbiol 2021 Sep 8:AEM0132721. Epub 2021 Sep 8.

Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.

The concept of bacterial dark matter stems from our inability to culture most microbes and represents a fundamental gap in our knowledge of microbial diversity. Herein we present the domestication of such an organism: a previously uncultured, novel species from the rare-Actinomycetes genus . Although initial recovery took >4 months, isolation of phenotypically distinct, domesticated generations occurred within weeks. Read More

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September 2021

Distinct genetic landscape and a low response to doxorubicin in a luminal-A breast cancer cell line of Pakistani origin.

Mol Biol Rep 2021 Sep 8. Epub 2021 Sep 8.

Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, ICCBS, University of Karachi, Karachi, 75270, Pakistan.

Background: Breast cancers exhibit genetic heterogeneity which causes differential responses to various chemotherapy agents. Given the unique demographic and genomic background in South Asia, genetic architecture in breast cancers is not fully explored.

Methods And Results: In this study, we determined the genetic landscape of our previously established luminal-A subtype breast cancer cell line (BC-PAK1), and compared it with a Caucasian origin MCF7 breast cancer cell line of the same molecular subtype. Read More

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September 2021

Type 2N VWD: Conclusions from the Spanish PCM-EVW-ES project.

Haemophilia 2021 Sep 7. Epub 2021 Sep 7.

Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain.

Introduction: Type 2N von Willebrand disease (VWD) is characterized by a decreased affinity of von Willebrand factor (VWF) for factor VIII (FVIII). Abnormal binding of FVIII to VWF (VWF:FVIIIB), results in low FVIII plasma levels, which can lead to a misdiagnosis of mild haemophilia A. Accurate diagnosis of type 2N VWD is essential for appropriate genetic counselling and therapy. Read More

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September 2021

Mutational landscape of marginal zone B-cell lymphomas of various origin: organotypic alterations and diagnostic potential for assignment of organ origin.

Virchows Arch 2021 Sep 8. Epub 2021 Sep 8.

Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland.

This meta-analysis aims to concisely summarize the genetic landscape of splenic, nodal and extranodal marginal zone lymphomas (MZL) in the dura mater, salivary glands, thyroid, ocular adnexa, lung, stomach and skin with respect to somatic variants. A systematic PubMed search for sequencing studies of MZL was executed. All somatic mutations of the organs mentioned above were combined, uniformly annotated, and a dataset containing 25 publications comprising 6016 variants from 1663 patients was created. Read More

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September 2021

Genomic and evolutionary classification of lung cancer in never smokers.

Nat Genet 2021 Sep 6;53(9):1348-1359. Epub 2021 Sep 6.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Lung cancer in never smokers (LCINS) is a common cause of cancer mortality but its genomic landscape is poorly characterized. Here high-coverage whole-genome sequencing of 232 LCINS showed 3 subtypes defined by copy number aberrations. The dominant subtype (piano), which is rare in lung cancer in smokers, features somatic UBA1 mutations, germline AR variants and stem cell-like properties, including low mutational burden, high intratumor heterogeneity, long telomeres, frequent KRAS mutations and slow growth, as suggested by the occurrence of cancer drivers' progenitor cells many years before tumor diagnosis. Read More

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September 2021

Binding affinity landscapes constrain the evolution of broadly neutralizing anti-influenza antibodies.

Elife 2021 Sep 7;10. Epub 2021 Sep 7.

Harvard University, Cambridge, United States.

Over the past two decades, several broadly neutralizing antibodies (bnAbs) that confer protection against diverse influenza strains have been isolated. Structural and biochemical characterization of these bnAbs has provided molecular insight into how they bind distinct antigens. However, our understanding of the evolutionary pathways leading to bnAbs, and thus how best to elicit them, remains limited. Read More

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September 2021

Nanopore sequencing approach for immunoglobulin gene analysis in chronic lymphocytic leukemia.

Sci Rep 2021 Sep 3;11(1):17668. Epub 2021 Sep 3.

Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", 70124, Bari, Italy.

The evaluation of the somatic hypermutation of the clonotypic immunoglobulin heavy variable gene has become essential in the therapeutic management in chronic lymphocytic leukemia patients. European Research Initiative on Chronic Lymphocytic Leukemia promotes good practices and standardized approaches to this assay but often they are labor-intensive, technically complex, with limited in scalability. The use of next-generation sequencing in this analysis has been widely tested, showing comparable accuracy and distinct advantages. Read More

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September 2021

Additive effects of variants of unknown significance in replication repair-associated DNA polymerase genes on mutational burden and prognosis across diverse cancers.

J Immunother Cancer 2021 Sep;9(9)

Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China

Background: Defects in replication repair-associated DNA polymerases often manifest an ultra-high tumor mutational burden (TMB), which is associated with higher probabilities of response to immunotherapies. The functional and clinical implications of different polymerase variants remain unclear.

Methods: Targeted next-generation sequencing using a 425-cancer gene panel, which covers all exonic regions of three polymerase genes (, , and ), was conducted in a cohort of 12,266 patients across 16 different tumor types from January 2017 to January 2019. Read More

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September 2021

Trio exome sequencing identified a novel de novo WASF1 missense variant leading to recurrent site substitution in a Chinese patient with developmental delay, microcephaly, and early-onset seizures: A mutational hotspot p.Trp161 and literature review.

Clin Chim Acta 2021 Aug 31;523:10-18. Epub 2021 Aug 31.

Department of Neurology, Children's Hospital of Soochow University, 92 Zhongnan Street, Suzhou Industrial Park, Suzhou 215025, Jiangsu, China. Electronic address:

Background: Neurodevelopmental disorder with absent language and variable seizures (NEDALVS, OMIM # 618707) is a newly described autosomal dominant condition caused by heterozygous de novo mutation in WASF1 gene. WASF1 is a key component of the WAVE regulatory complex (WRC) required for actin polymerization. So far, only 3 distinct truncating variants clustering at the WCA domain, 3 missense variants localized to the meander region and a copy number variant (CNV) of WASF1 have been identified among 11 NEDALVS cases previously reported. Read More

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Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype.

Blood Adv 2021 Sep 3. Epub 2021 Sep 3.

Leiden University Medical Center, Leiden, Netherlands.

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. 103 O-DLBCL patients were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB). Read More

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September 2021

Clonal dynamics of circulating tumor DNA during immune checkpoint blockade therapy for melanoma.

Cancer Sci 2021 Sep 3. Epub 2021 Sep 3.

Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.

Assessment of treatment efficacy of immune checkpoint inhibitors in melanoma patients is difficult since the response to these therapies varies among patients or lesions. The clonal evolution of cancer during immune checkpoint blockade therapy could cause treatment resistance. We investigated the potential of liquid biopsy in monitoring the mutational profiles of metastatic melanoma during immunotherapy. Read More

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September 2021

Comprehensive molecular profiling to predict clinical outcomes in pancreatic cancer.

Ther Adv Med Oncol 2021 28;13:17588359211038478. Epub 2021 Aug 28.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.

Background: Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among common cancers. The genomic landscape of PDAC is defined by four mutational pathways: ( (), (), and (). However, there is a paucity of data on the molecular features associated with clinical outcomes after surgery or chemotherapy. Read More

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Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease.

BMC Gastroenterol 2021 Sep 1;21(1):339. Epub 2021 Sep 1.

Department of Infectious Diseases, Institute of Hepatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China.

Aim: To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype-phenotype correlation in a large-scale sample of Chinese WD patients.

Methods: One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Read More

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September 2021

Genetic and immune characteristics of sentinel lymph node metastases and multiple lymph node metastases compared to their matched primary breast tumours.

EBioMedicine 2021 Aug 25;71:103542. Epub 2021 Aug 25.

Department of Breast Cancer, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China; School of Medicine, South China University of Technology, 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China;; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China;; Shantou University Medical College, Shantou, Guangdong, China. Electronic address:

Background: Patients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).

Methods: Genomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. Read More

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Genomic landscape and tumor mutational burden determination of circulating tumor DNA in over 5,000 Chinese lung cancer patients.

Clin Cancer Res 2021 Aug 26. Epub 2021 Aug 26.

Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xi'an Jiaotong University

Purpose: Having emerged as a non-invasive and clinically applicable approach for molecular determination of lung cancer, a genomic overview of ctDNA of large-scale cohort may be helpful in novel biomarker development and therapeutic innovation.

Experimental Design: Primary cohort encompasses 5,671 blood samples from 4,892 lung cancer patients. Pairwise tissue samples from 579 patients and additional 358 sample pairs were collected to evaluate the correlation between blood and tissue TMB. Read More

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Tumour Genome Characterization of a Rare Case of Pulmonary Enteric Adenocarcinoma and Prior Colon Adenocarcinoma.

J Pers Med 2021 Aug 4;11(8). Epub 2021 Aug 4.

Genomic Oncology Research Group, Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland.

Pulmonary enteric adenocarcinoma (PEAC) is a rare variant of lung adenocarcinoma first described in the early 1990s in a lung tumour with overlapping lung and small intestine features. It is a rare tumour with fewer than 300 cases described in the published literature and was only formally classified in 2011. Given these characteristics the diagnosis is challenging, but even more so in a patient with prior gastrointestinal malignancy. Read More

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The Genetics of Myelodysplastic Syndromes: Clinical Relevance.

Genes (Basel) 2021 Jul 27;12(8). Epub 2021 Jul 27.

IRCCS Humanitas Research Hospital, Via Alessandro Manzoni 56, 20089 Rozzano, Italy.

Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of genetic mutations that results in heterogeneous clinical phenotype and outcome. Genetic studies have enabled the identification of a set of recurrently mutated genes which are central to the pathogenesis of MDS and can be organized into a limited number of cellular pathways, including RNA splicing (, , , genes), DNA methylation (, , ), transcription regulation (), signal transduction (, ), DNA repair (), chromatin modification (, ), and cohesin complex (). Read More

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Genome-derived Classification Signature for Ampullary Adenocarcinoma to Improve Clinical Cancer Care.

Clin Cancer Res 2021 Aug 25. Epub 2021 Aug 25.

Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering Cancer Center

Background: The clinical behavior of ampullary adenocarcinoma varies widely. Targeted tumor sequencing may better define biologically distinct subtypes to improve diagnosis and management.

Methods: The hidden genome algorithm, a multilevel meta-feature regression model, was trained on a prospectively sequenced cohort of 3,411 patients (1,001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, 2,245 colorectal adenocarcinoma) and subsequently applied to targeted panel DNA sequencing data from ampullary adenocarcinomas. Read More

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The RBS1 domain of Gemin5 is intrinsically unstructured and interacts with RNA through conserved Arg and aromatic residues.

RNA Biol 2021 Aug 23:1-11. Epub 2021 Aug 23.

Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Madrid.

Gemin5 is a multifaceted RNA-binding protein that comprises distinct structural domains, including a WD40 and TPR-like for which the X-ray structure is known. In addition, the protein contains a non-canonical RNA-binding domain (RBS1) towards the C-terminus. To understand the RNA binding features of the RBS1 domain, we have characterized its structural characteristics by solution NMR linked to RNA-binding activity. Read More

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Structural and Genomic Insights Into Pyrazinamide Resistance in Underlie Differences Between Ancient and Modern Lineages.

Front Mol Biosci 2021 23;8:619403. Epub 2021 Jul 23.

Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Resistance to drugs used to treat tuberculosis disease (TB) continues to remain a public health burden, with missense point mutations in the underlying bacteria described for nearly all anti-TB drugs. The post-genomics era along with advances in computational and structural biology provide opportunities to understand the interrelationships between the genetic basis and the structural consequences of mutations linked to drug resistance. Pyrazinamide (PZA) is a crucial first line antibiotic currently used in TB treatment regimens. Read More

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Distinct Mutational Processes Influence Germline DNA Mutations.


Cancer Discov 2021 Aug 20. Epub 2021 Aug 20.

Nine distinct mutational processes underlie human germline mutations. Read More

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