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https://www.readbyqxmd.com/read/28543997/the-mutational-frequency-of-braf-and-kras-in-low-grade-serous-testicular-neoplasms-a-case-series
#1
Paidamwoyo Gwiti, Ildikó Vereczkey, David Cundell, Shazia Aslam, Tim Clench, Jeremy Braybrooke, Muhammed Sohail, Zsombor Melegh
AIMS: Low grade serous neoplasms of the testis are rare neoplasms that demonstrate striking morphological similarities with the better-understood ovarian neoplasms. The cell of origin, relation to serous ovarian tumour and the pathogenesis of these neoplasms are not fully established. METHODS AND RESULTS: As low grade serous ovarian neoplasms are known to harbour mutations in the MAP-kinase pathway, we investigated the involvement of BRAF and KRAS mutations in low grade testicular serous tumour by way of mutational analysis of 7 cases...
May 19, 2017: Histopathology
https://www.readbyqxmd.com/read/28540987/lack-of-aberrant-methylation-in-an-adjacent-area-of-left-sided-colorectal-cancer
#2
Otgontuya Sambuudash, Hyun Soo Kim, Mee Yon Cho
PURPOSE: The molecular nature and the rate-limiting step of epigenetic field defects in the evolution of left-sided colorectal cancer (LCA) remain uncertain. MATERIALS AND METHODS: The methylation status of 27 candidate field defect markers, six classic CpG island methylator phenotype (CIMP) markers, and LINE-1 were determined in LCA and adjacent normal mucosas (ADJs) from 33 LCA patients and in left normal colorectal mucosa (LNM) from 33 age- and sex-matched controls...
July 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28539463/braf-fusion-as-a-novel-mechanism-of-acquired-resistance-to-vemurafenib-in-braf-v600e-mutant-melanoma
#3
Atul Kulkarni, Husam Al-Hraishawi, Srilatha Simhadri, Kim M Hirshfield, Suzie Chen, Sharon R Pine, Chandrika Jeyamohan, Levi Sokol, Siraj M Ali, Man Lung Teo, Eileen White, Lorna Rodriguez-Rodriguez, Janice M Mehnert, Shridar Ganesan
Many patients with BRAF (V)(600E) mutant melanoma treated with BRAF inhibitors experience a rapid response, but ultimately develop resistance. Insight into the mechanism of resistance is critical for development of more effective treatment strategies. <br /><br />Experimental Design: Comprehensive genomic profiling of serial biopsies was performed in a patient with a BRAF(V600E) mutant metastatic melanoma who developed resistance to vemurafenib. An AGAP3-BRAF fusion gene, identified in the vemurafenib-resistant tumor, was expressed in BRAF(V600E) melanoma cell lines and its effect on drug sensitivity was evaluated...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28538413/a-long-term-survivor-with-esophageal-melanoma-and-pulmonary-metastasis-after-single-stage-esophagectomy-and-lobectomy-case-report-and-literature-review
#4
Tian Zhao, Feng-Wei Kong, Heng Wang, Dong Liu, Chun-Ying Wang, Jin-Hua Luo, Miao Zhang, Wen-Bin Wu
RATIONALE: The optimal therapeutic regimen for primary malignant melanoma of the esophagus (PMME) need to be further elucidated. Besides, the efficacy of surgery for PMME with remote metastasis is uncertain for its rarity. PATIENT CONCERNS: Herein a previously healthy patient was admitted for dysphagia and fatigue, without significant weight loss. DIAGNOSES: The pathological and molecular tests revealed his diagnosis of BRAF-mutant, advanced PMME with localized pulmonary metastasis...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28537891/multiplex-pcr-approach-to-simultaneously-identify-several-mutations-in-fine-needle-cytology-thyroid-samples
#5
Emilia Vuttariello, Marco Borra, Elvira Mauriello, Celeste Calise, Barbara D'Andrea, Anna Capiluongo, Franco Fulciniti, Anna Cipolletta, Mario Monaco, Luciano Pezzullo, Gennaro Chiappetta
The most frequent initial manifestation of thyroid cancer is the appearance of a nodule. More than 20% of the general population has a palpable thyroid nodule and the percentage rises to 70% based on ultrasound identification. In 95% of cases the nodule is simply a hyperplastic or benign lesion. The most reliable diagnostic test for thyroid nodules is fine needle aspiration (FNA), but cytological discrimination between malignant and benign follicular neoplasms remains difficult. Cytological analysis is now, almost routinely, being combined with molecular genetics to enable the pathologist to make a more objective diagnosis...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537807/next-generation-sequencing-identifies-gene-mutations-that-are-predictive-of-malignancy-in-residual-needle-rinses-collected-from-fine-needle-aspirations-of-thyroid-nodules
#6
Maren Y Fuller, Dina Mody, April Hull, Kristi Pepper, Heather Hendrickson, Randall Olsen
CONTEXT: - Thyroid nodules have a prevalence of approximately 70% in adults. Fine-needle aspiration (FNA) is a minimally invasive, cost-effective, standard method to collect tissue from thyroid nodules for cytologic examination. However, approximately 15% of thyroid FNA specimens cannot be unambiguously diagnosed as benign or malignant. OBJECTIVE: - To investigate whether clinically actionable data can be obtained using next-generation sequencing of residual needle rinse material...
May 24, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28533998/ipilimumab-as-a-cause-of-severe-pan-colitis-and-colonic-perforation
#7
Raj Shah, Danielle Witt, Talal Asif, Fahad F Mir
Ipilimumab is a human monoclonal antibody that functions as a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor that is used to treat malignant melanoma. Due to ipilimumab's removal of immune regulation, specifically through the inactivation of CTLA-4, it is commonly associated with inflammatory and autoimmune events. Gastrointestinal (GI) related immune-related adverse events such as diarrhea occur in 29% of patients with 7.6% of patients specifically suffering from colitis. We describe a case of colonic perforation with ipilimumab use...
April 20, 2017: Curēus
https://www.readbyqxmd.com/read/28526721/health-care-resource-utilization-and-associated-costs-among-metastatic-cutaneous-melanoma-patients-treated-with-ipilimumab-intuition-study
#8
Grant A McArthur, Peter Mohr, Paolo Antonio Ascierto, Ana Arance, Ana Banos Hernaez, Peter Kaskel, Michael Weichenthal, Reshma Shinde, Kendall Stevinson
BACKGROUND: There are limited real-world data on health care resource utilization (HCRU) among advanced melanoma patients. The objective of this study was to describe HCRU and health care costs associated with the management of advanced melanoma patients receiving ipilimumab. METHODS: This retrospective multinational, observational study included advanced melanoma patients from Australia, Germany, Italy, and Spain who had received at least 1 dose of ipilimumab. Data extracted from medical charts included inpatient admissions, outpatient visits, surgical procedures, laboratory investigations, radiation therapy, imaging studies, and concomitant medications...
May 19, 2017: Oncologist
https://www.readbyqxmd.com/read/28525297/association-analysis-of-nonsyndromic-congenital-heart-disease-and-tag-single-nucleotide-polymorphisms-of-tbx20-and-genes-in-the-ras-mapk-pathway
#9
Zhiling Luo, Yan Shen, Wei Chen, Xuejuan Ma, Liping Liu, Xiaoqin Huang, Zhaoqing Yang, Hao Sun
AIMS: The present study was performed to determine whether there are variants in TBX20 and genes of the Ras-MAPK pathway associated with nonsyndromic congenital heart disease (ns-CHD). MATERIALS AND METHODS: A total of 223 ns-CHD patients and 273 healthy controls from China were selected as study subjects to perform an association analysis using 22 tag single-nucleotide polymorphisms (tag SNPs) located either in one of three genes in the Ras-MAPK pathway (MAP2K2, BRAF, and RAF1) or the TBX20 gene that have previously been associated with syndromic congenital heart disease...
May 19, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28521635/pathologic-characteristics-natural-history-and-prognostic-implications-of-braf-v600e-mutation-in-pediatric-papillary-thyroid-carcinoma
#10
Steven Hardee, Manju L Prasad, Pei Hui, Catherine A Dinauer, Raffaella A Morotti
The BRAF(V600E) mutation is the most common genetic aberration in papillary thyroid cancer (PTC), found in up to 68% of PTC in adults where it is associated with aggressive features. The incidence of this mutation in pediatric PTC is less frequent, reported as 0%-20% in the past and up to 63% in one recent series. Data suggest the mutation is not associated with an aggressive course in children; however, there are limited numbers of reported case series, so the prognostic implications remain poorly understood...
June 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28521461/kras-and-braf-mutations-in-serum-exosomes-from-patients-with-colorectal-cancer-in-a-chinese-population
#11
Yi-Xin Hao, Yong-Mei Li, Ming Ye, Yan-Yan Guo, Qiu-Wen Li, Xiu-Mei Peng, Qi Wang, Shu-Fang Zhang, Hui-Xia Zhao, He Zhang, Guang-Hui Li, Jian-Hua Zhu, Wen-Hua Xiao
The efficacy of epidermal growth factor receptor- targeted therapy is significantly associated with Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-raf serine/threonine kinase proto-oncogene (BRAF) mutation in patients with colorectal cancer (CRC), for which the standard gene testing is currently performed using tumor tissue DNA. The aim of the present study was to compare the presence of KRAS and BRAF mutations in the serum exosome and primary tumor tissue from patients with CRC. Genomic DNA were extracted from the tumor tissues of 35 patients with histologically-confirmed CRC and exosomal mRNA were obtained from peripheral blood, which were collected from the corresponding patients prior to surgery...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515244/what-when-and-how-of-biomarker-testing-in-non-small-cell-lung-cancer
#12
Gregory L Riely
Biomarker testing is recommended for all patients diagnosed with non-small cell lung cancer. At a minimum, testing should include the mutations/fusions EGFR, ALK, ROS1, and the protein programmed death ligand-1 (PD-L1), because FDA-approved therapies are available for these alterations. Other actionable molecular findings include RET rearrangements, BRAF(V600E) mutations, and MET exon 14 alterations. If adequate testing was not performed at treatment initiation, molecular testing should be performed before administration of subsequent lines of therapy...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28513830/association-between-mutations-of-critical-pathway-genes-and-survival-outcomes-according-to-the-tumor-location-in-colorectal-cancer
#13
Dae-Won Lee, Sae-Won Han, Yongjun Cha, Jeong Mo Bae, Hwang-Phill Kim, Jaemyun Lyu, Hyojun Han, Hyoki Kim, Hoon Jang, Duhee Bang, Iksoo Huh, Taesung Park, Jae-Kyung Won, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Tae-You Kim
BACKGROUND: Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. METHODS: Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy...
May 17, 2017: Cancer
https://www.readbyqxmd.com/read/28506411/partial-thyroidectomy-for-papillary-thyroid-microcarcinoma-is-completion-total-thyroidectomy-indicated
#14
C Dobrinja, M Pastoricchio, M Troian, F Da Canal, S Bernardi, B Fabris, N de Manzini
AIM: Papillary thyroid microcarcinoma (PTMC) is increasing in incidence. Despite its excellent clinical outcomes, there is still debate regarding which surgical approach is more appropriate for PTMC, procedures including hemithyroidectomy (HT), total thyroidectomy (TT), and completion thyroidectomy (CT) after initial HT and histopathologic examination confirming a PTMC. Here we report our experience in the surgical management of PTMC. METHODS: We conducted a retrospective evaluation of all patients who received a postoperative diagnosis of PTMC between January 2001 and January 2016...
May 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28501764/open-label-multicentre-safety-study-of-vemurafenib-in%C3%A2-3219-patients-with-braf-v600-mutation-positive-metastatic-melanoma-2-year-follow-up-data-and-long-term-responders-analysis
#15
Christian U Blank, James Larkin, Ana M Arance, Axel Hauschild, Paola Queirolo, Michele Del Vecchio, Paolo A Ascierto, Ivana Krajsova, Jacob Schachter, Bart Neyns, Claus Garbe, Vanna Chiarion Sileni, Mario Mandalà, Helen Gogas, Enrique Espinosa, Geke A P Hospers, Wilson H Miller, Susan Robson, Martina Makrutzki, Vladan Antic, Michael P Brown
BACKGROUND: The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF(V600) mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety. METHODS: This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas(®) 4800 BRAF V600 Mutation Test)...
May 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28500561/study-of-%C3%AE-catenin-and-braf-alterations-in-adamantinomatous-and-papillary-craniopharyngiomas-mutation-analysis-with-immunohistochemical-correlation-in-54-cases
#16
Prit Benny Malgulwar, Aruna Nambirajan, Pankaj Pathak, Mohammed Faruq, Vaishali Suri, Chitra Sarkar, Amandeep Jagdevan, Bhawani Shankar Sharma, Mehar Chand Sharma
Craniopharyngiomas (CP) are rare benign epithelial tumors, with two histological variants, namely the adamantinomatous variant (ACP) and the rarer papillary variant (PCP). They are locally infiltrative and surgically challenging tumors with severe long term morbidity. CTNNB1 mutations with β-catenin immunopositivity and BRAFV600E mutations with anti-VE immunopositivity have been recently described in ACPs and PCPs respectively. We aimed to study BRAF and CTNNB1 gene mutations in CPs operated at our institute, and correlate it with clinicopathological parameters including histopathology and immunohistochemistry (IHC) for proteins VE-1 and β-catenin...
May 12, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28489587/ngs-based-identification-of-mutational-hotspots-for-targeted-therapy-in-anaplastic-thyroid-carcinoma
#17
Vera Tiedje, Saskia Ting, Thomas Herold, Sarah Synoracki, Soeren Latteyer, Lars C Moeller, Denise Zwanziger, Martin Stuschke, Dagmar Fuehrer, Kurt Werner Schmid
CONTEXT: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive carcinomas with no consistent survival benefit when treated with conventional radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are increasingly explored and first promising results have been reported in single case studies. OBJECTIVE: To determine the prevalence of mutations in known thyroid oncogenes and signalling pathways amendable to targeted therapy in a large cohort of ATC...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28480077/combined-dabrafenib-and-trametinib-treatment-in-a-case-of-chemotherapy-refractory-extrahepatic-braf-v600e-mutant-cholangiocarcinoma-dramatic-clinical-and-radiological-response-with-a-confusing-synchronic-new-liver-lesion
#18
Judit Kocsis, Anita Árokszállási, Csilla András, Ingrid Balogh, Edit Béres, Júlia Déri, István Peták, Levente Jánváry, Zsolt Horváth
Since the prognosis of advanced cholangiocarcinoma (CCA) remains poor with traditional chemotherapy, attention has shifted to molecularly targeted agents. Results of available clinical studies reveal little or no benefit of using targeted agents in advanced CCA. Limitations of these trials could be the lack of comprehensive molecular and genetic characterization of CCA samples in order to identify potential drug targets. Here we report a case of a 59-year-old female with chemotherapy-refractor, metastatic extrahepatic cholangiocarcinoma (EHCCA)...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28475299/consistency-and-reproducibility-of-next-generation-sequencing-and-other-multigene-mutational-assays-a-worldwide-ring-trial-study-on-quantitative-cytological-molecular-reference-specimens
#19
Umberto Malapelle, Clara Mayo-de-Las-Casas, Miguel A Molina-Vila, Rafael Rosell, Spasenija Savic, Michel Bihl, Lukas Bubendorf, Manuel Salto-Tellez, Dario de Biase, Giovanni Tallini, David H Hwang, Lynette M Sholl, Rajyalakshmi Luthra, Birgit Weynand, Sara Vander Borght, Edoardo Missiaglia, Massimo Bongiovanni, Daniel Stieber, Philippe Vielh, Fernando Schmitt, Alessandra Rappa, Massimo Barberis, Francesco Pepe, Pasquale Pisapia, Nicola Serra, Elena Vigliar, Claudio Bellevicine, Matteo Fassan, Massimo Rugge, Carlos E de Andrea, Maria D Lozano, Fulvio Basolo, Gabriella Fontanini, Yuri E Nikiforov, Suzanne Kamel-Reid, Gilda da Cunha Santos, Marina N Nikiforova, Sinchita Roy-Chowdhuri, Giancarlo Troncone
BACKGROUND: Molecular testing of cytological lung cancer specimens includes, beyond epidermal growth factor receptor (EGFR), emerging predictive/prognostic genomic biomarkers such as Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral [v-ras] oncogene homolog (NRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA). Next-generation sequencing (NGS) and other multigene mutational assays are suitable for cytological specimens, including smears...
May 5, 2017: Cancer
https://www.readbyqxmd.com/read/28472910/helix-coil-transition-signatures-braf-v600e-mutation-and-virtual-screening-for-inhibitors-directed-against-mutant-braf
#20
Srinivas Bandaru, Tharaparambil Gangadharan Sumithnath, Saphy Sharda, Sanskruti Lakhotia, Anudeep Sharma, Amrita Jain, Tajamul Hussain, Anuraj Nayarisseri, Sanjeev Kumar Singh
Mutation in the B RAF at V600E has been well implicated in the carcinogenesis that makes it as an attractive therapeutic target. In the present study, we sought to identify the basis of V600E mutation at functional and structural grounds. The study also pursues to identify a candidate molecule with better pharmacological profiles than existing BRAF inhibitors through computational approaches. The functional effects of V600E mutation was predicted using SIFT and Polyphen servers. Protein structural alterations were predicted using SDM server and RMSD calculations...
May 2, 2017: Current Drug Metabolism
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