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https://www.readbyqxmd.com/read/28631713/-braf-positive-paucicellular-variant-of-anaplastic-carcinoma-in-the-presence-of-tall-cell-variant-papillary-thyroid-cancer
#1
O V Dolzhansky, E M Paltseva, D N Khmelkova, F A Konovalov, I V Kanivets, A V Lavrov, D V Pyankov, S A Korostelev, O A Levendyuk, V M Pominalnaya, D N Fedorov
To paper describes a case of paucicellular anaplastic cancer in the presence of tall cell variant papillary thyroid carcinoma. Microscopic examination showed that the differentiated component of the tumor was composed of papillary structures with tall cells, the height of which exceeded 3-4 times the width. Its anaplastic component consisted of fibrous tissue with occasional spindle-shaped cells and focal lymphocytic infiltration to the extent of 70%. The spindle-shaped cells expressed cytokeratins, β-catenin, p53, and vimentin...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28630054/slc45a2-a-melanoma-antigen-with-high-tumor-selectivity-and-reduced-potential-for-autoimmune-toxicity
#2
Jungsun Park, Amjad H Talukder, Seonah Lim, Kwanghee Kim, Ke Pan, Brenda Melendez, Sherille D Bradley, Kyle Jackson, Jahan S Khalili, Junmei Wang, Caitlin Creasy, Bih-Fang Pan, Scott E Woodman, Chantale Bernatchez, David Hawke, Patrick Hwu, Kyung-Mi Lee, Jason Roszik, Gregory Lizee, Cassian Yee
Cytotoxic T lymphocyte (CTL)-based immunotherapies have had remarkable success at generating objective clinical responses in patients with advanced metastatic melanoma.  Although the melanocyte differentiation antigens (MDAs) MART-1, PMEL, and tyrosinase were among the first melanoma tumor-associated antigens identified and targeted with immunotherapy, expression within normal melanocytes of the eye and inner ear can elicit serious autoimmune side effects, thus limiting their clinical potential as CTL targets...
June 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28625643/sequential-liquid-biopsies-reveal-dynamic-alterations-of-egfr-driver-mutations-and-indicate-egfr-amplification-as-a-new-mechanism-of-resistance-to-osimertinib-in-nsclc
#3
Franciele H Knebel, Fabiana Bettoni, Andrea K Shimada, Manoel Cruz, João Victor Alessi, Marcelo V Negrão, Luiz Fernando L Reis, Artur Katz, Anamaria A Camargo
Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge. Sequential liquid biopsies were used to monitor a patient with EGFR-exon19del positive NSCLC, who received erlotinib and progressed through the acquisition of the EGFR-T790M mutation...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28622068/salmonella-typhimurium-a1-r-targeting-of-a-chemotherapy-resistant-braf-v600e-melanoma-in-a-patient-derived-orthotopic-xenograft-pdox-model-is-enhanced-in-combination-with-either-vemurafenib-temozlomide
#4
Kei Kawaguchi, Kentaro Igarashi, Bartosz Chmielowski, Takashi Murakami, Tasuku Kiyuna, Ming Zhao, Yong Zhang, Scott D Nelson, Tara A Russell, Sarah M Dry, Arun S Singh, Yunfeng Li, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
A metastatic melanoma obtained from the right chest wall of a patient was previously established orthotopically in the right chest wall of nude mice as a patient-derived orthotopic xenograft (PDOX) model. We previously showed that the combination of tumor targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) and chemotherapy was highly effective against the melanoma PDOX. In the present study, we investigated the mechanism of the high efficacy of this combination. Two weeks after implantation, 40 PDOX mouse models were randomized into four groups of 10 mice each: untreated control (n = 10); treated with S...
June 16, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28617917/genomic-profiling-of-small-bowel-adenocarcinoma
#5
Alexa B Schrock, Craig E Devoe, Robert McWilliams, James Sun, Thomas Aparicio, Philip J Stephens, Jeffrey S Ross, Richard Wilson, Vincent A Miller, Siraj M Ali, Michael J Overman
Importance: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking. Objective: To perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations. Design, Setting, and Participants: Prospective analysis was performed of clinical samples from patients with SBA (n = 317), colorectal cancer (n = 6353), and gastric carcinoma (n = 889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions...
June 15, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28617912/mutation-in-braf-v600e-reply
#6
Frank A Sinicrope, Qian Shi, Steven R Alberts
No abstract text is available yet for this article.
June 15, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28617898/mutation-in-braf-v600e-a-poor-prognostic-marker-in-stage-iii-colon-cancers-with-deficient-mmr
#7
Sheik Emambux, Guillaume Mouillet, David Tougeron
No abstract text is available yet for this article.
June 15, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28614984/tert-promoter-mutations-were-not-found-in-papillary-thyroid-microcarcinomas-that-showed-disease-progression-on-active-surveillance
#8
Tomonori Yabuta, Michiko Matsuse, Mitsuyoshi Hirokawa, Shunichi Yamashita, Norisato Mitsutake, Akira Miyauchi
BACKGROUND: Papillary thyroid carcinoma (PTC) generally has an indolent course, and non-operative management is acknowledged for papillary thyroid microcarcinoma (PTMC). However, some PTMCs progress and we cannot predict future progression at their presentation. BRAF and TERT promoter mutations were recently reported to be associated with poor outcomes of PTC. Here we sought to determine whether these mutations are associated with the progression of PTMCs, toward the goal of predicting progression/nonprogression...
June 14, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28611198/phase-i-dose-escalation-and-expansion-study-of-the-braf-inhibitor-encorafenib-lgx818-in-metastatic-braf-mutant-melanoma
#9
Jean-Pierre Delord, Caroline Robert, Marta Nyakas, Grant A McArthur, Ragini Kudchakar, Amit Mahipal, Yasuhide Yamada, Ryan J Sullivan, Ana Arance, Richard F Kefford, Matteo S Carlino, Manuel Hidalgo, Carlos Gomez-Roca, Daniela Michel, Abdelkader Seroutou, Vassilios Aslanis, Giordano Caponigro, Darrin Stuart, Laure Moutouh-de Parseval, Tim Demuth, Reinhard Dummer
Purpose: Encorafenib, a selective BRAF-inhibitor (BRAFi), has a pharmacological profile that is distinct from that of other clinically active BRAFis. We evaluated encorafenib in a phase I study in patients with BRAFi treatment-naive and pretreated BRAF-mutant melanoma. <p>Experimental Design: The pharmacological activity of encorafenib was first characterized preclinically. Encorafenib monotherapy was then tested across a range of once-daily (QD; 50-700mg) or twice-daily (75-150mg) regimens in a phase I, open-label, dose-escalation and -expansion study in adult patients with histologically confirmed advanced/metastatic BRAF-mutant melanoma...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28607685/concurrent-braf-and-pten-mutations-in-melanoma-of-unknown-origin-presenting-as-a-breast-mass
#10
Emmanuel Agosto-Arroyo, Marilin Rosa, Alec Chau, Laila Khazai
BACKGROUND: Metastases represent a small percentage of the malignancies affecting the breast, and only 5% of melanomas originate from non-cutaneous sites. Multiple genetic aberrations have been associated with the development of melanocytic lesions, including BRAF V600E mutation. Mutations in PTEN gene have also been related to the pathogenesis of multiple malignancies. PURPOSE/METHOD: This is the case of a 28-year-old female who presented with a tender, palpable mass in the upper outer quadrant of the right breast...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28604751/melanocytic-nevi-and-melanoma-unraveling-a-complex-relationship
#11
REVIEW
W E Damsky, M Bosenberg
Approximately 33% of melanomas are derived directly from benign, melanocytic nevi. Despite this, the vast majority of melanocytic nevi, which typically form as a result of BRAF(V600E)-activating mutations, will never progress to melanoma. Herein, we synthesize basic scientific insights and data from mouse models with common observations from clinical practice to comprehensively review melanocytic nevus biology. In particular, we focus on the mechanisms by which growth arrest is established after BRAF(V600E) mutation...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28597080/intratumoral-fusobacterium-nucleatum-abundance-correlates-with-macrophage-infiltration-and-cdkn2a-methylation-in-microsatellite-unstable-colorectal-carcinoma
#12
Hye Eun Park, Jung Ho Kim, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang
Fusobacterium nucleatum (Fn), a specific species of gut microbiota, has been suggested to be enriched in the microsatellite instability-high (MSI-H) molecular subtype of colorectal carcinomas (CRCs). However, the clinicopathologic and molecular factors that interact with Fn in MSI-H CRCs are poorly understood. In this study, 16S ribosomal RNA gene DNA sequence of Fn was quantitatively measured by real-time polymerase chain reaction in tumor DNA samples from a total of 160 surgically resected MSI-H CRC tissues...
June 8, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28596664/bullous-pyoderma-gangrenosum-associated-with-hairy-cell-leukemia-and-its-complete-response-to-cladribine-therapy
#13
Ankur Jain, Deepesh Lad, Gaurav Prakash, Alka Khadwal, Pankaj Malhotra, Amanjit Bal, Nabhajit Mallik, Narendar Kumar, Subhash Varma
Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis seen in association with systemic disorders including hematologic malignancies. Hairy cell leukemia (HCL) however, is an unusual association of PG. We describe a 49-year old lady who presented to our hematology clinic with easy fatiguability and ulcerative skin lesions of 6 months duration. Examination revealed pallor and massive splenomegaly. Indurated, ulcerated lesion with undermined edges and necrotic base was observed on left thigh. Investigations revealed pancytopenia and bone marrow examination identified typical hairy cells...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28595733/a-novel-cytogenetic-and-molecular-characterization-of-renal-metanephric-adenoma-identification-of-partner-genes-involved-in-translocation-t-9-15-p24-q24
#14
Aida Catic, Amina Kurtovic-Kozaric, Sarah H Johnson, George Vasmatzis, Michael R Pins, Jillene Kogan
Renal metanephric adenoma (MA) is a rare benign tumor frequently misclassified when microscopic features alone are applied. The correct classification of a renal tumor is critical for diagnostic, prognostic, and therapeutic purposes. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to MA development have been recognized. Recent data suggest that 90% of MA have BRAF(V600E) mutations; the genetics of the remaining 10% are unclear. To date, only one case of a chromosomal translocation, t(9;15)(p24;q24) associated with MA has been reported...
August 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28595656/ros-production-induced-by-braf-inhibitor-treatment-rewires-metabolic-processes-affecting-cell-growth-of-melanoma-cells
#15
Giulia Cesi, Geoffroy Walbrecq, Andreas Zimmer, Stephanie Kreis, Claude Haan
BACKGROUND: Most melanoma patients with BRAF(V600E) positive tumors respond well to a combination of BRAF kinase and MEK inhibitors. However, some patients are intrinsically resistant while the majority of patients eventually develop drug resistance to the treatment. For patients insufficiently responding to BRAF and MEK inhibitors, there is an ongoing need for new treatment targets. Cellular metabolism is such a promising new target line: mutant BRAF(V600E) has been shown to affect the metabolism...
June 8, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28595259/molecular-profiling-of-signet-ring-cell-colorectal-cancer-provides-a-strong-rationale-for-genomic-targeted-and-immune-checkpoint-inhibitor-therapies
#16
Muhammad A Alvi, Maurice B Loughrey, Philip Dunne, Stephen McQuaid, Richard Turkington, Marc-Aurel Fuchs, Claire McGready, Victoria Bingham, Brendan Pang, Wendy Moore, Perry Maxwell, Mark Lawler, Jacqueline A James, Graeme I Murray, Richard H Wilson, Manuel Salto-Tellez
BACKGROUND: Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease. METHODS: Using test (n=26) and validation (n=18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1...
June 8, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28592763/malignant-lymphoma-pathophysiology-and-current-therapy
#17
Koji Izutsu
Recent advances in the understanding of molecular pathogenesis of lymphoma have enabled us to clearly define disease entity by means of a disease-specific gene mutation and to select candidates for novel targeted therapy. In this review three different clinically relevant topics related to the molecular pathogenesis of lymphoma were covered. In the 2016 revision of the World Health Organization classification of lymphoid malignancies, firstly, disease-specific mutations such as MYD88 L265P in Waldenström macroglobulinemia and BRAF V600E in hairy cell leukemia were incorporated into diagnostic tests, and secondly, the determination of cell-of-origin in diffuse large B-cell lymphoma (DLBCL) was strongly recommended in diagnosis...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28592387/dabrafenib-plus-trametinib-in-patients-with-braf-v600-mutant-melanoma-brain-metastases-combi-mb-a-multicentre-multicohort-open-label-phase-2-trial
#18
Michael A Davies, Philippe Saiag, Caroline Robert, Jean-Jacques Grob, Keith T Flaherty, Ana Arance, Vanna Chiarion-Sileni, Luc Thomas, Thierry Lesimple, Laurent Mortier, Stergios J Moschos, David Hogg, Iván Márquez-Rodas, Michele Del Vecchio, Céleste Lebbé, Nicolas Meyer, Ying Zhang, Yingjie Huang, Bijoyesh Mookerjee, Georgina V Long
BACKGROUND: Dabrafenib plus trametinib improves clinical outcomes in BRAF(V600)-mutant metastatic melanoma without brain metastases; however, the activity of dabrafenib plus trametinib has not been studied in active melanoma brain metastases. Here, we report results from the phase 2 COMBI-MB trial. Our aim was to build on the current body of evidence of targeted therapy in melanoma brain metastases through an evaluation of dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases...
June 2, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28586760/clinical-mutational-profiling-of-1006-lung-cancers-by-next-generation-sequencing
#19
Peter B Illei, Deborah Belchis, Li-Hui Tseng, Doreen Nguyen, Federico De Marchi, Lisa Haley, Stacy Riel, Katie Beierl, Gang Zheng, Julie R Brahmer, Frederic B Askin, Christopher D Gocke, James R Eshleman, Patrick M Forde, Ming-Tseh Lin
Analysis of lung adenocarcinomas for actionable mutations has become standard of care. Here, we report our experience using next generation sequencing (NGS) to examine AKT1, BRAF, EGFR, ERBB2, KRAS, NRAS, and PIK3CA genes in 1006 non-small cell lung cancers in a clinical diagnostic setting. NGS demonstrated high sensitivity. Among 760 mutations detected, the variant allele frequency (VAF) was 2-5% in 33 (4.3%) mutations and 2-10% in 101 (13%) mutations. A single bioinformatics pipeline using Torrent Variant Caller, however, missed a variety of EGFR mutations...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28585075/disease-progression-in-papillary-thyroid-cancer-with-biochemical-incomplete-response-to-initial-therapy
#20
Nicole K Zern, Roderick Clifton-Bligh, Anthony J Gill, Ahmad Aniss, Stan Sidhu, Leigh Delbridge, Diana Learoyd, Bruce Robinson, Mark Sywak
BACKGROUND: Dynamic risk stratification is utilized in the follow-up of patients with papillary thyroid carcinoma (PTC). Analysis of outcomes after biochemical incomplete response (BIR) to initial therapy will allow better individualization of care. METHODS: A total of 494 patients with PTC were followed prospectively. Immunohistochemistry (IHC) for BRAF(V600E) mutation was completed on all surgical specimens. After exclusion of patients with inadequate data, 353 patients were stratified into four categories of response to initial therapy: excellent, biochemical incomplete, structural incomplete, or indeterminate...
June 5, 2017: Annals of Surgical Oncology
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