keyword
MENU ▼
Read by QxMD icon Read
search

Kmt2d

keyword
https://www.readbyqxmd.com/read/28404210/characteristics-of-epilepsy-in-patients-with-kabuki-syndrome-with-kmt2d-mutations
#1
Naoko Kurahashi, Noriko Miyake, Seiji Mizuno, Eriko Koshimizu, Hirokazu Kurahashi, Keitaro Yamada, Jun Natsume, Yusuke Aoki, Miho Nakamura, Hiroko Taniai, Yuki Maki, Chihiro Abe-Hatano, Naomichi Matsumoto, Koichi Maruyama
BACKGROUND: The characteristics of epilepsy in patients with Kabuki syndrome with KMT2D mutations (KABUK1) have not yet been well documented. This is the first review to explore this. MATERIALS & METHODS: We enrolled 14 patients with KABUK1, whose median age was 13.6years (range=4.1-21.3years). Their medical records from October 1981 to May 2016 were retrospectively analyzed. RESULTS: Epilepsy was present in 5 (36%) patients. Four of these patients presented with nonsense mutations and one with missense mutations...
April 9, 2017: Brain & Development
https://www.readbyqxmd.com/read/28389907/targeted-next-generation-sequencing-identified-novel-mutations-in-triple-negative-myeloproliferative-neoplasms
#2
Yu-Cheng Chang, Huan-Chau Lin, Yi-Hao Chiang, Caleb Gon-Shen Chen, Ling Huang, Wei-Ting Wang, Chun-Chia Cheng, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Shu-Jen Chen, Ken-Hong Lim, Yuan-Yeh Kuo
Mutations in JAK2, MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28375985/distinct-functions-of-histone-h3-lysine-4-methyltransferases-in-normal-and-malignant-hematopoiesis
#3
Weiwei Yang, Patricia Ernst
PURPOSE OF REVIEW: Histone H3, lysine 4 (H3K4) methylation is one chromatin modification that defines distinct regulatory states of euchromatin. Mammals express six main histone methyltransferase (HMT) enzymes that modify H3K4 by monomethylation, dimethylation or trimethylation. Recent studies examine roles of some of these HMTs and their cofactors in hematopoiesis and leukemia. We discuss these emerging studies together with prior embryonic stem data, revealing how these enzymes function...
April 1, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28363912/pi3k-signaling-regulates-er-activity-via-kmt2d-in-er-breast-cancer
#4
(no author information available yet)
Targeting PI3Kα enhances KMT2D methyltransferase activity to promote ER-mediated transcription.
March 31, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28336670/pi3k-pathway-regulates-er-dependent-transcription-in-breast-cancer-through-the-epigenetic-regulator-kmt2d
#5
Eneda Toska, Hatice U Osmanbeyoglu, Pau Castel, Carmen Chan, Ronald C Hendrickson, Moshe Elkabets, Maura N Dickler, Maurizio Scaltriti, Christina S Leslie, Scott A Armstrong, José Baselga
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)-positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28329645/frequent-somatic-mutations-of-chromatin-remodeling-genes-in-metastatic-cutaneous-squamous-cell-carcinoma
#6
Amanda Ewart Toland
Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but is typically correlated with high survival rates and low rates of metastasis. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals are estimated to die yearly from this disease. As it is difficult to predict which cSCCs are more likely to metastasize, and because there are no targeted therapies specifically designated for metastatic cSCC, we performed exome and targeted sequencing of 18 metastatic and 10 primary cSCCs to identify mutations with potential therapeutic benefit...
September 15, 2016: Dermatology Online Journal
https://www.readbyqxmd.com/read/28302137/mutations-of-crebbp-and-socs1-are-independent-prognostic-factors-in-diffuse-large-b-cell-lymphoma-mutational-analysis-of-the-sakk-38-07-prospective-clinical-trial-cohort
#7
Darius Juskevicius, David Jucker, Dirk Klingbiel, Christoph Mamot, Stephan Dirnhofer, Alexandar Tzankov
BACKGROUND/PURPOSE: Recently, the mutational background of diffuse large B cell lymphoma (DLBCL) has been revealed, identifying specific genetic events that drive lymphomagenesis. However, the prognostic value of these mutations remains to be determined. Prognostic biomarkers in DLBCL are urgently needed, since the current clinical parameter-based factors (e.g., International Prognostic Index (IPI)) are insufficient, particularly in identifying patients with poor prognosis who might benefit from alternative treatments...
March 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28295206/molecular-clinical-and-neuropsychological-study-in-31-patients-with-kabuki-syndrome-and-kmt2d-mutations
#8
Natacha Lehman, Anne Claire Mazery, Antoine Visier, Clarisse Baumann, Dominique Lachesnais, Yline Capri, Annick Toutain, Sylvie Odent, Myriam Mikaty, Cyril Goizet, Emmanuelle Taupiac, Marie Line Jacquemont, Elodie Sanchez, Elise Schaefer, Vincent Gatinois, Laurence Faivre, Delphine Minot, Honorine Kayirangwa, Kim-Hanh Le Qang Sang, Nathalie Boddaert, Sophie Bayard, Didier Lacombe, Sébastien Moutton, Isabelle Touitou, Marlène Rio, Jeanne Amiel, Stanislas Lyonnet, Damien Sanlaville, Marie Christine Picot, David Geneviève
Kabuki syndrome (KS - OMIM 147920) is a rare developmental disease characterized by the association of multiple congenital anomalies and intellectual disability. This study aimed to investigate intellectual performance in children with Kabuki syndrome and link the performance to several clinical features and molecular data. We recruited 31 children with KMT2D mutations who were 6 to 16 years old. They all completed the Weschler Intelligence Scale for Children, fourth edition. We calculated all indexes: the Full Scale Intellectual Quotient (FSIQ), Verbal Comprehension Index (VCI), Perceptive Reasoning Index (PRI), Processing Speed Index (PSI), and Working Memory Index (WMI)...
March 14, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28256057/interrupted-bipartite-clavicle-as-a-diagnostic-clue-in-kabuki-syndrome
#9
Maria Haanpää, Helena Schlecht, Gauri Batra, Jill Clayton-Smith, Sofia Douzgou
Kabuki syndrome is a rare developmental disorder characterized by typical facial features, postnatal growth deficiency, mild to moderate intellectual disability, and minor skeletal anomalies. It is caused by mutations of the KMT2D and KDM6A genes while recently RAP1A and RAP1B mutations have been shown to rarely contribute to the pathogenesis. We report two patients' presentation of Kabuki syndrome caused by different KMT2D mutations, both including an interrupted/bipartite clavicle. The clinical diagnosis of Kabuki syndrome may be challenging, especially in younger patients and we suggest that the observation of a bipartite clavicle may be an additional diagnostic clue to prompt investigation for Kabuki syndrome...
March 3, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28249646/chromosomal-abnormalities-and-molecular-landscape-of-metastasizing-mucinous-salivary-adenocarcinoma
#10
Alex Panaccione, Yi Zhang, Yanfang Mi, Yoshitsugu Mitani, Guo Yan, Manju L Prasad, W Hayes McDonald, Adel K El-Naggar, Wendell G Yarbrough, Sergey V Ivanov
BACKGROUND: Mucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-based therapies...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28152507/the-mutational-landscape-of-ocular-marginal-zone-lymphoma-identifies-frequent-alterations-in-tnfaip3-followed-by-mutations-in-tbl1xr1-and-crebbp
#11
Hyunchul Jung, Hae Yong Yoo, Seung Ho Lee, Sohyun Shin, Sang Cheol Kim, Sejoon Lee, Je-Gun Joung, Jae-Yong Nam, Daeun Ryu, Jae Won Yun, Jung Kyoon Choi, Ambarnil Ghosh, Kyeong Kyu Kim, Seok Jin Kim, Won Seog Kim, Woong-Yang Park, Young Hyeh Ko
Ocular marginal zone lymphoma is a common type of low-grade B-cell lymphoma. To investigate the genomic changes that occur in ocular marginal zone lymphoma, we analyzed 10 cases of ocular marginal zone lymphoma using whole-genome and RNA sequencing and an additional 38 cases using targeted sequencing. Major genetic alterations affecting genes involved in nuclear factor (NF)-κB pathway activation (60%), chromatin modification and transcriptional regulation (44%), and B-cell differentiation (23%) were identified...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28139835/unraveling-molecular-pathways-shared-by-kabuki-and-kabuki-like-syndromes
#12
REVIEW
C Lintas, A M Persico
Kabuki syndrome (KS) is a rare genetic syndrome characterized by a typical facial gestalt, variable degrees of intellectual disability, organ malformations, postnatal growth retardation and skeletal abnormalities. So far, KMT2D or KDM6A mutation has been identified as the main cause of KS, accounting for 56%-75% and 3%-8% of cases, respectively. Patients without mutations in 1 of the 2 causative KS genes are often referred to as affected by Kabuki-like syndrome. Overall, they represent approximately 30% of KS cases, pointing toward substantial genetic heterogeneity for this condition...
January 31, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28106467/follicular-lymphoma-a-b-cell-malignancy-addicted-to-epigenetic-mutations
#13
Koorosh Korfi, Sara Ali, James A Heward, Jude Fitzgibbon
While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28029553/somatic-mutation-detection-using-various-targeted-detection-assays-in-paired-samples-of-circulating-tumor-dna-primary-tumor-and-metastases-from-patients-undergoing-resection-of-colorectal-liver-metastases
#14
Nick Beije, Jean C Helmijr, Marjolein J A Weerts, Corine M Beaufort, Matthew Wiggin, Andre Marziali, Cornelis Verhoef, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR)...
October 10, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28027012/dynamic-chromatin-regulation-at-notch-target-genes
#15
Benedetto Daniele Giaimo, Franz Oswald, Tilman Borggrefe
RBPJ is the central transcription factor that controls the Notch-dependent transcriptional response by coordinating repressing histone H3K27 deacetylation and activating histone H3K4 methylation. Here, we discuss the molecular mechanisms how RBPJ interacts with opposing NCoR/HDAC-corepressing or KMT2D/UTX-coactivating complexes and how this is controlled by phosphorylation of chromatin modifiers.
January 2017: Transcription
https://www.readbyqxmd.com/read/28013028/h3k4-methyltransferase-activity-is-required-for-mll4-protein-stability
#16
Younghoon Jang, Chaochen Wang, Lenan Zhuang, Chengyu Liu, Kai Ge
Transcriptional enhancers play a key role in cell type-specific gene expression and cell fate transition. Enhancers are marked by histone H3K4 mono- and di-methylation (H3K4me1/2). The tumor suppressor MLL4 (KMT2D) is a major enhancer H3K4 mono- and di-methyltransferase with a partial functional redundancy with MLL3 (KMT2C). However, the functional role of MLL4 enzymatic activity remains elusive. To address this issue, we have generated MLL4 enzyme-dead knock-in (KI) embryonic stem (ES) cells and mice, which carry Y5477A/Y5523A/Y5563A mutations in the enzymatic SET domain of the MLL4 protein...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28007623/small-cell-lung-cancer-exhibits-frequent-inactivating-mutations-in-the-histone-methyltransferase-kmt2d-mll2-calgb-151111-alliance
#17
Arnaud Augert, Qing Zhang, Breanna Bates, Min Cui, Xiaofei Wang, Gary Wildey, Afshin Dowlati, David MacPherson
INTRODUCTION: SCLC is a lethal neuroendocrine tumor type that is highly prone to metastasis. There is an urgency to understand the mutated genes that promote SCLC, as there are no approved targeted therapies yet available. SCLC is rarely resected, limiting the number of samples available for genomic analyses of somatic mutations. METHODS: To identify potential driver mutations in human SCLC we sequenced the whole exomes of 18 primary SCLCs and seven cell lines along with matched normal controls...
April 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27999180/a-ketogenic-diet-rescues-hippocampal-memory-defects-in-a-mouse-model-of-kabuki-syndrome
#18
Joel S Benjamin, Genay O Pilarowski, Giovanni A Carosso, Li Zhang, David L Huso, Loyal A Goff, Hilary J Vernon, Kasper D Hansen, Hans T Bjornsson
Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d(+/βGeo)). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27997699/chromatin-remodelling-and-dna-repair-genes-are-frequently-mutated-in-endometrioid-endometrial-carcinoma
#19
Pablo García-Sanz, Juan Carlos Triviño, Alba Mota, María Pérez López, Eva Colás, Alejandro Rojo-Sebastián, Ángel García, Sonia Gatius, María Ruiz, Jaime Prat, Rafael López-López, Miguel Abal, Antonio Gil-Moreno, Jaume Reventós, Xavier Matias-Guiu, Gema Moreno-Bueno
In developed countries, endometrial carcinoma is the most common cancer that affects the female genital tract. Endometrial carcinoma is divided into two main histological types, type I or endometrioid and type II or non-endometrioid, each of which have characteristic, although not exclusive, molecular alterations and mutational profiles. Nevertheless, information about the implication and relevance of some of these genes in this disease is lacking. We sought here to identify new recurrently mutated genes in endometrioid cancers that play a role in tumourigenesis and that influence the clinical outcome...
April 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27991736/kmt2d-p-gln3575his-segregating-in-a-family-with-autosomal-dominant-choanal-atresia-strengthens-the-kabuki-charge-connection
#20
Lauren Badalato, Sali M K Farhan, Allison A Dilliott, Dennis E Bulman, Robert A Hegele, Sharan L Goobie
Choanal atresia is rarely reported in Kabuki syndrome, but is a common feature of CHARGE syndrome. Otherwise, the two conditions have a number of overlapping features, and the molecular links between them have recently been elucidated. Here, we report a case of a mother and her two children who presented with congenital choanal atresia. We performed whole exome sequencing on DNA from the mother and her two unaffected parents, and identified a de novo, novel variant in KMT2D. KMT2D p.Gln3575His segregated with disease status in the family, and is associated with a unique and conserved phenotype in the affected family members, with features overlapping with Kabuki and CHARGE syndromes...
January 2017: American Journal of Medical Genetics. Part A
keyword
keyword
22443
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"