Read by QxMD icon Read

somatic mutations

Shi Yang, Dominick A Leone, Asok Biswas, April Deng, Drazen Jukic, Rajendra Singh, Uma Sundram, Meera Mahalingam
Despite the efficacy of BRAF-targeted and PD-L1-related immune therapies in tackling metastatic melanoma, a significant number of patients exhibit resistance. Given this, the objective of the current study was to ascertain concordance of somatic mutations in BRAF/ NRAS/TERT and, immunohistochemical PD-L1 and CD8 in matched primary cutaneous and metastatic melanoma. A total of 43 archival paired samples with sufficient material for genetic and immunohistochemical analyses met criteria for inclusion in the study...
August 15, 2018: Human Pathology
Ya-Sian Chang, Chun-Chi Chang, Hsi-Yuan Huang, Chien-Yu Lin, Kun-Tu Yeh, Jan-Gowth Chang
Genetic and epigenetic alterations are associated with the progression and prognosis of medullary thyroid carcinoma (MTC). We performed whole-exome sequencing of tumor tissue from seven patients with sporadic MTC using an Illumina HiSeq 2000 sequencing system. We conducted Sanger sequencing to confirm the somatic mutations in both tumor and matched normal tissues. We applied Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis with the Database for Annotation, Visualization, and Integrated Discovery and STRING for pathway analysis...
August 17, 2018: Endocrine Pathology
Barbara Hernando, Viki B Swope, Steven Guard, Renny J Starner, Kevin Choi, Ayesha Anwar, Pamela Cassidy, Sancy Leachman, Ana Luisa Kadekaro, Dorothy C Bennett, Zalfa A Abdel-Malek
Co-inheritance of germline mutation in cyclin-dependent kinase inhibitor 2A (CDKN2A) and loss-of-function (LOF) melanocortin 1 receptor (MC1R) variants is clinically associated with exaggerated risk for melanoma. To understand the combined impact of these mutations, we established and tested primary human melanocyte cultures from different CDKN2A mutation carriers, expressing either wild-type MC1R or MC1R LOF variant(s). These cultures expressed the CDKN2A product p16 (INK4A) and functional MC1R. Except for 32ins24 mutant melanocytes, the remaining cultures showed no detectable aberrations in proliferation or capacity for replicative senescence...
August 16, 2018: Pigment Cell & Melanoma Research
Vincent Jonchere, Laetitia Marisa, Malorie Greene, Alain Virouleau, Olivier Buhard, Romane Bertrand, Magali Svrcek, Pascale Cervera, Anastasia Goloudina, Erell Guillerm, Florence Coulet, Samuel Landman, Toky Ratovomanana, Sylvie Job, Mira Ayadi, Nabila Elarouci, Lucile Armenoult, Fatiha Merabtene, Sylvie Dumont, Yann Parc, Jérémie H Lefèvre, Thierry André, Jean-François Fléjou, Agathe Guilloux, Ada Collura, Aurélien de Reyniès, Alex Duval
Background & Aims: Recent studies have shown that cancers arise as a result of the positive selection of driver somatic events in tumor DNA, with negative selection playing only a minor role, if any. However, these investigations were concerned with alterations at nonrepetitive sequences and did not take into account mutations in repetitive sequences that have very high pathophysiological relevance in the tumors showing microsatellite instability (MSI) resulting from mismatch repair deficiency investigated in the present study...
2018: Cellular and Molecular Gastroenterology and Hepatology
Mingzhe Xu, Zhongmeng Zhao, Xuanping Zhang, Aiqing Gao, Shuyan Wu, Jiayin Wang
Gene fusion structure is a class of common somatic mutational events in cancer genomes, which are often formed by chromosomal mutations. Identifying the driver gene(s) in a fusion structure is important for many downstream analyses and it contributes to clinical practices. Existing computational approaches have prioritized the importance of oncogenes by incorporating prior knowledge from gene networks. However, different methods sometimes suffer different weaknesses when handling gene fusion data due to multiple issues such as fusion gene representation, network integration, and the effectiveness of the evaluation algorithms...
August 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Uri Rozovski, Michael J Keating, Zeev Estrov
The immunoglobulin heavy chain gene (IgHV) mutation status correlates with the clinical outcome of patients with chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy. Why the survival rate of patients with unmutated IgHV is worse than that of patients with mutated IgHV is unknown. CLL cells with unmutated IgHV were thought to originate from naïve B lymphocytes, whereas CLL cells with mutated IgHV were thought to arise from B cells that have undergone somatic hypermutation (SHM). Cell surface protein expression profile and gene expression studies showing that all CLL cells, regardless of their IgHV mutation status, are of postgerminal center origin, negated this hypothesis...
August 16, 2018: Acta Haematologica
Gaël Nicolas, Rocio Acuna-Hidalgo, Michael J Keogh, Olivier Quenez, Marloes Steehouwer, Stefan Lelieveld, Stéphane Rousseau, Anne-Claire Richard, Manon S Oud, Florent Marguet, Annie Laquerrière, Chris M Morris, Johannes Attems, Colin Smith, Olaf Ansorge, Safa Al Sarraj, Thierry Frebourg, Dominique Campion, Didier Hannequin, David Wallon, Christian Gilissen, Patrick F Chinnery, Joris A Veltman, Alexander Hoischen
INTRODUCTION: A minority of patients with sporadic early-onset Alzheimer's disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes such as APP, PSEN1, or PSEN2. We hypothesized that negatively screened patients may harbor somatic variants in these genes. METHODS: We applied an ultrasensitive approach based on single-molecule molecular inversion probes followed by deep next generation sequencing of 11 genes to 100 brain and 355 blood samples from 445 sporadic patients with AD (>80% exhibited an early onset, <66 years)...
August 13, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Ferenc Kálovits, Márton Tompa, Ádám Nagy, Bernadette Kálmán
Background and purpose: Oncogenesis is related to a sequential accumulation of somatic mutations. Comprehensive characterizations of the genomic landscapes have been completed recently for several tumors, glioblastoma being among the first ones. Our own translational research studies have been focused on defining molecular subtypes of glioblastoma in the clinical setting because of an expected prognostic and therapeutic utility of the information. Somatic mutations in genes of the isocitrate dehydrogenase (IDH) enzyme family appear to be among the best-defined biomarkers that also influence tumor behavior and confer clinical utility...
July 30, 2018: Ideggyógyászati Szemle
Juliane Lippert, Silke Appenzeller, Raimunde Liang, Silviu Sbiera, Stefan Kircher, Barbara Altieri, Indrajit Nanda, Isabel Weigand, Andrea Gehrig, Sonja Steinhauer, Renzo J M Riemens, Andreas Rosenwald, Clemens R Müller, Matthias Kroiss, Simone Rost, Martin Fassnacht, Cristina L Ronchi
Context: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis and current medical therapies have limited efficacy in its advanced stages. Genome-wide multi-omics-studies identified molecular patterns associated with clinical outcome. Objective: Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine. Design: 117 tumor samples from 107 ACC patients were analyzed...
August 2, 2018: Journal of Clinical Endocrinology and Metabolism
Susana Llerena, Nuria García-Díaz, Soraya Curiel-Olmo, Antonio Agraz-Doblas, Agustín García-Blanco, Helena Pisonero, María Varela, Miguel Santibáñez, Carmen Almaraz, Laura Cereceda, Nerea Martínez, María Teresa Arias-Loste, Ángela Puente, Luis Martín-Ramos, Carlos Rodríguez de Lope, Federico Castillo-Suescun, Carmen Cagigas-Fernandez, Pablo Isidro, Carlos Lopez-López, Marcos Lopez-Hoyos, Javier Llorca, Jesús Agüero, Benedicto Crespo-Facorro, Ignacio Varela, Miguel Ángel Piris, Javier Crespo, José Pedro Vaqué
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There is increasing interest in developing specific markers to serve as predictors of response to sorafenib and to guide targeted therapy. Using a sequencing platform designed to study somatic mutations in a selection of 112 genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell lines, and to use the data to study the biological and mechanistic effects of case-specific targeted therapies used alone or in combination with sorafenib...
July 20, 2018: Oncotarget
Elena Drosopoulou, Dimitris Vlastos, Ioanna Efthimiou, Paraskevi Kyrizaki, Sofia Tsamadou, Maria Anagnostopoulou, Danai Kofidou, Maxim Gavriilidis, Despoina Mademtzoglou, Penelope Mavragani-Tsipidou
Chios mastic products are well-known for their broad applications in food industry, cosmetics, and healthcare since the antiquity. Given our recent finding that Chios mastic water (CMW) exerts antigenotoxic action, in the present study, we evaluated the genotoxic as well as the antigenotoxic potential of the four major compounds of CMW, namely, verbenone, α-terpineol, linalool, and trans-pinocarveol. The cytokinesis block micronucleus (CBMN) assay in cultured human lymphocytes and the Drosophila Somatic Mutation And Recombination Test (SMART), also known as the wing spot test, were employed...
August 15, 2018: Scientific Reports
Yan-Bin Pang, Ping Wu, Luo-Ming Hua, Xin DU, Jing Wang
The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myelogenous leukemia (AML). The treatment of MDS is highly dependent on the reliability of the prognostic evaluation model. Current clinical prognostic scoring systems are comprised of morphology, pivotal clinical trials and cytogenetic findings. However, none of the available prognostic systems incorporates disease-related molecular abnormalities, such as somatic mutations...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Markus W Löffler, Julia Steinhilber, Franz J Hilke, Sebastian P Haen, Hans Bösmüller, Ivonne-Aidee Montes-Mojarro, Irina Bonzheim, Antje Stäbler, Ulrike Faust, Ute Grasshoff, Ingmar Königsrainer, Hans-Georg Rammensee, Lothar Kanz, Alfred Königsrainer, Stefan Beckert, Olaf Riess, Christopher Schroeder
BACKGROUND: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported...
August 15, 2018: BMC Medical Genetics
Kazuaki Suda, Hirofumi Nakaoka, Kosuke Yoshihara, Tatsuya Ishiguro, Ryo Tamura, Yutaro Mori, Kaoru Yamawaki, Sosuke Adachi, Tomoko Takahashi, Hiroaki Kase, Kenichi Tanaka, Tadashi Yamamoto, Teiichi Motoyama, Ituro Inoue, Takayuki Enomoto
Endometriosis is characterized by ectopic endometrial-like epithelium and stroma, of which molecular characteristics remain to be fully elucidated. We sequenced 107 ovarian endometriotic and 82 normal uterine endometrial epithelium samples isolated by laser microdissection. In both endometriotic and normal epithelium samples, numerous somatic mutations were identified within genes frequently mutated in endometriosis-associated ovarian cancers. KRAS is frequently mutated in endometriotic epithelium, with a higher mutant allele frequency (MAF) accompanied by arm-level allelic imbalances...
August 14, 2018: Cell Reports
Safoura Ghalamkari, Farinaz Khosravian, Hamidreza Mianesaz, Mohammad Kazemi, Mohaddeseh Behjati, Sayyed Mohammadreza Hakimian, Mansoor Salehi
One of the most common somatic mutations in breast cancer is found in PIK3CA with a prevalence rate of 18-45%. Different variants of this gene are considered as resistance markers for treatment with HER2-targeted medicines. Conventional molecular methods such as Sanger sequencing are not able to detect mutations with low abundance in a mixture of wild-type DNA, especially in the early stages of cancer development. In this study, two methods of co-amplification at lower denaturation temperature PCR (COLD-PCR) and high-resolution melting (HRM) were combined for detection of mutations in exon 9 of PIK3CA; DNA, therefore, was extracted from MCF-7 and BT-474 as mutant and wild-type cell lines respectively...
August 15, 2018: Applied Biochemistry and Biotechnology
Zheng Zhu, Zhigang Liang, Jichun Tong, Xiaoliang Mao, Yajun Yin, Lydia C Manor, Zhenya Shen
Ethnicity differences may contribute to the variety of overall survival in pulmonary adenocarcinoma, while the influence of ethnicity relevant somatic driver mutations (ERSDM) profile on Caucasian survival is not well investigated. In this study, we studied epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and Serine/Threonine Kinase 11 (STK11) to construct the ERSDM profile. Those genes were selected as harboring somatic driver mutations with >10% prevalence and with different occurrence between Caucasian and Asian ethnicity...
July 2018: Saudi Journal of Biological Sciences
Johanna Kondelin, Kari Salokas, Lilli Saarinen, Kristian Ovaska, Heli Rauanheimo, Roosa-Maria Plaketti, Jiri Hamberg, Xiaonan Liu, Leena Yadav, Alexandra E Gylfe, Tatiana Cajuso, Ulrika A Hänninen, Kimmo Palin, Heikki Ristolainen, Riku Katainen, Eevi Kaasinen, Tomas Tanskanen, Mervi Aavikko, Minna Taipale, Jussi Taipale, Laura Renkonen-Sinisalo, Anna Lepistö, Selja Koskensalo, Jan Böhm, Jukka-Pekka Mecklin, Halit Ongen, Emmanouil T Dermitzakis, Outi Kilpivaara, Pia Vahteristo, Mikko Turunen, Sampsa Hautaniemi, Sari Tuupanen, Auli Karhu, Niko Välimäki, Markku Varjosalo, Esa Pitkänen, Lauri A Aaltonen
Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI colorectal cancers (CRCs), however, also contain more point mutations than microsatellite-stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV Somatic point mutation data from the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and respective normals, and 12 whole-genome-sequenced sporadic MSI CRCs and respective normals were utilized...
August 14, 2018: EMBO Molecular Medicine
TaeHyung Kim, Joon Ho Moon, Jae-Sook Ahn, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Seung Hyun Choi, Ja-Yeon Lee, Marc S Tyndel, Myung-Geun Shin, Yoo Jin Lee, Sang Kyun Sohn, Seong-Kyu Park, Zhaolei Zhang, Hyeoung-Joon Kim, Dennis Dong Hwan Kim
Next generation sequencing (NGS) has been applied to define clinically relevant somatic mutations and classify subtypes in acute myeloid leukemia (AML). Persistent allelic burden after chemotherapy is associated with higher relapse incidence, but presence of allelic burden in AML patients after receiving allogeneic hematopoietic cell transplantation (HCT) has not been examined longitudinally. As such, we aimed to assess the feasibility of NGS in monitoring AML patients receiving HCT. Using targeted gene panel, we performed NGS in 104 AML patients receiving HCT using samples collected at diagnosis, pre-HCT, and post-HCT at day 21...
August 14, 2018: Blood
Matthew L Carlson, James B Smadbeck, Michael J Link, Eric W Klee, George Vasmatzis, Lisa A Schimmenti
OBJECTIVES: 1) Describe the genetic alterations discovered in a series of sporadic vestibular schwannomas (VS). 2) Identify if more clinically aggressive variants possess different genetic alterations compared to more indolent-behaving VS. METHODS: Fresh frozen tumor and matched peripheral blood leukocytes from 23 individuals with sporadic VS were analyzed using whole-exome sequencing, tumor whole transcriptome expression profiling (mRNA-Seq), and tumor mate-pair analysis...
August 13, 2018: Otology & Neurotology
Graziela Z Dal Molin, Shannon N Westin, Robert L Coleman
Rucaparib is a potent inhibitor of poly (ADP-ribose) polymerase (PARP) PARP1, PARP2 and PARP3, and to a lesser extent, PARP4, PARP10, PARP12, PARP15 and PARP16. Study 10 and ARIEL2 evaluated the use of rucaparib as treatment in patients with recurrent high-grade ovarian carcinoma and resulting in approval of rucaparib for patients with both germline and somatic BRCA mutation. Data from the Phase III trial ARIEL3 led to approval in platinum-sensitive disease as maintenance. This article reviews the efficacy, safety, pharmacokinetics and pharmacodynamics of rucaparib as well as future and ongoing trials...
August 14, 2018: Future Oncology
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"