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https://www.readbyqxmd.com/read/28550040/kras-g12d-expression-in-lung-resident-myeloid-cells-promotes-pulmonary-lch-like-neoplasm-sensitive-to-statin-treatment
#1
Tamihiro Kamata, Susan Giblett, Catrin Pritchard
Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm associated with somatic mutations in the genes involved in the RAF/MEK/ERK signaling pathway. Recently, oncogenic mutations in NRAS/KRAS, upstream regulators of the RAF/MEK/ERK pathway, have been reported in pulmonary, but not in non-pulmonary, LCH cases, suggesting organ-specific contribution of oncogenic RAS to LCH pathogenesis. Using a mouse model expressing KRAS(G12D) in the lung by nasal delivery of adenoviral Cre, here we show that KRAS(G12D) expression in lung-resident myeloid cells induces pulmonary LCH-like neoplasms comprised of pathogenic CD11c(high)F4/80+CD207+ cells...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549037/evaluation-of-a-dna-extraction-and-purification-protocol-using-archived-formalin-fixed-paraffin-embedded-tissues-for-braf-mutations-analysis-in-papillary-thyroid-microcarcinomas
#2
Adela Nechifor-Boilă, Andrada Loghin, Françoise Descotes, Myriam Decaussin-Petrucci, Angela Borda
The isolation of good quality genomic DNA from formalin-fixed, paraffin-embedded tissues is challenging, especially in cases of small tissue specimens. The aim of our study was to evaluate a DNA extraction protocol using formalin-fixed, paraffin-embedded tissues in our laboratory and apply this method to a series of papillary thyroid microcarcinomas (PTMCs). A total of 25 PTMCs and 3 papillary thyroid carcinoma control cases were included in the study. We assessed a DNA extraction protocol on the basis of a precipitation method (MasterPure DNA purification kit, Epicentre), according to the manufacturer's instructions...
May 25, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28548101/corrigendum-targeting-bmk1-impairs-the-drug-resistance-to-combined-inhibition-of-braf-and-mek1-2-in-melanoma
#3
Chengli Song, Lina Wang, Qiang Xu, Kai Wang, Dan Xie, Zhe Yu, Kui Jiang, Lujian Liao, John R Yates, Jiing-Dwan Lee, Qingkai Yang
This corrects the article DOI: 10.1038/srep46244.
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28547128/low-grade-spinal-glioneuronal-tumors-with-braf-gene-fusion-and-1p-deletion-but-without-leptomeningeal-dissemination
#4
Jason C H Chiang, Julie H Harreld, Brent A Orr, Suash Sharma, Azzam Ismail, Annette D Segura, David W Ellison
No abstract text is available yet for this article.
May 25, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#5
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28545134/structures-of-the-inactive-and-active-states-of-rip2-kinase-inform-on-the-mechanism-of-activation
#6
Erika Pellegrini, Luca Signor, Saurabh Singh, Elisabetta Boeri Erba, Stephen Cusack
Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K) is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles...
2017: PloS One
https://www.readbyqxmd.com/read/28544821/predictive-model-for-high-frequency-microsatellite-instability-in-colorectal-cancer-patients-over-50%C3%A2-years-of-age
#7
Kenji Fujiyoshi, Tatsuro Yamaguchi, Miho Kakuta, Akemi Takahashi, Yoshiko Arai, Mina Yamada, Gou Yamamoto, Sachiko Ohde, Misato Takao, Shin-Ichiro Horiguchi, Soichiro Natsume, Shinsuke Kazama, Yusuke Nishizawa, Yoji Nishimura, Yoshito Akagi, Hirohiko Sakamoto, Kiwamu Akagi
Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high-frequency MSI (MSI-H)...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28544061/survival-difference-according-to-mutation-status-in-a-prospective-cohort-study-of-australian-patients-with-metastatic-non-small-cell-lung-carcinoma-nsclc
#8
Lavinia Tan, Marliese Alexander, Ann Officer, Michael MacManus, Linda Mileshkin, Ross Jennens, Dishan Herath, Richard de Boer, Stephen B Fox, David Ball, Benjamin Solomon
BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histologic subtypes but also different molecular subtypes. Our objective is to describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled onto a prospective Thoracic Malignancies Cohort (TMC) Study between July 2012 and August 2016 were selected...
May 24, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28543997/the-mutational-frequency-of-braf-and-kras-in-low-grade-serous-testicular-neoplasms-a-case-series
#9
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/28543697/molecular-insights-into-melanoma-brain-metastases
#10
REVIEW
Dana Westphal, Isabella C Glitza Oliva, Heike Niessner
Substantial proportions of patients with metastatic melanoma develop brain metastases during the course of their disease, often resulting in significant morbidity and death. Despite recent advances with BRAF/MEK and immune-checkpoint inhibitors in the treatment of patients who have melanoma with extracerebral metastases, patients who have melanoma brain metastases still have poor overall survival, highlighting the need for further therapy options. A deeper understanding of the molecular pathways involved in the development of melanoma brain metastases is required to develop more brain-specific therapies...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28543695/mechanisms-and-strategies-to-overcome-resistance-to-molecularly-targeted-therapy-for-melanoma
#11
REVIEW
Su Yin Lim, Alexander M Menzies, Helen Rizos
The identification of driver mutations in melanoma has changed the field of cancer treatment. BRAF and NRAS mutations are predominant in melanoma and lead to overactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Selective inhibitors targeting key effectors of the MAPK pathway have revolutionized the treatment of patients with advanced metastatic BRAF-mutant melanoma. However, resistance to therapy is almost universal and remains a major challenge in clinical care, with the majority of patients progressing within 1 year...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28542846/cpg-island-methylator-phenotype-identifies-high-risk-patients-among-microsatellite-stable-braf-mutated-colorectal-cancers
#12
Hege Marie Vedeld, Marianne Merok, Marine Jeanmougin, Stine A Danielsen, Hilde Honne, Gro Kummeneje Presthus, Aud Svindland, Ole H Sjo, Merete Hektoen, Mette Eknaes, Arild Nesbakken, Ragnhild A Lothe, Guro E Lind
The prognostic value of CpG island methylator phenotype (CIMP) in colorectal cancer remains unsettled. We aimed to assess the prognostic value of this phenotype analyzing a total of 1126 tumor samples obtained from two Norwegian consecutive colorectal cancer series. CIMP status was determined by analyzing the 5-markers CAGNA1G, IGF2, NEUROG1, RUNX3 and SOCS1 by quantitative methylation specific PCR (qMSP). The effect of CIMP on time to recurrence (TTR) and overall survival (OS) were determined by uni- and multivariate analyses...
May 20, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28540987/lack-of-aberrant-methylation-in-an-adjacent-area-of-left-sided-colorectal-cancer
#13
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
#14
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/28539323/etv1-positive-cells-give-rise-to-brafv600e-mutant-gastrointestinal-stromal-tumors
#15
Leili Ran, Devan Murphy, Jessica Sher, Zhen Cao, Shangqian Wang, Edward Walczak, Youxin Guan, Yuanyuan Xie, Shipra Shukla, Yu Zhan, Cristina R Antonescu, Yu Chen, Ping Chi
Gastrointestinal Stromal Tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA-wild type GIST, including mutant BRAF-driven tumors, have been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis...
May 24, 2017: 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
#16
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/28538219/molecular-alterations-in-patients-with-pulmonary-adenocarcinoma-presenting-with-malignant-pleural-effusion-at-the-first-diagnosis
#17
Erika F Rodriguez, Maryam Shabihkhani, Jamal Carter, Zahra Maleki
OBJECTIVES: The aim of this study was to report cytologic and molecular features of pulmonary adenocarcinoma patients presenting with a malignant pleural effusion at the first diagnosis. STUDY DESIGN: Patients who had a cytopathologic diagnosis conclusive for lung adenocarcinoma for the first time on their pleural fluid specimen, and molecular testing done, were studied. The control group consisted of patients with a malignant pleural effusion that developed during disease progression...
May 25, 2017: Acta Cytologica
https://www.readbyqxmd.com/read/28537912/braf-mek-inhibitors-promote-cd47-expression-that-is-reversible-by-erk-inhibition-in-melanoma
#18
Fen Liu, Chen Chen Jiang, Xu Guang Yan, Hsin-Yi Tseng, Chun Yan Wang, Yuan Yuan Zhang, Hamed Yari, Ting La, Margaret Farrelly, Su Tang Guo, Rick F Thorne, Lei Jin, Qi Wang, Xu Dong Zhang
The expression of CD47 on the cancer cell surface transmits "don't eat me" signalling that not only inhibits phagocytosis of cancer cells by phagocytes but also impairs anti-cancer T cell responses. Here we report that oncogenic activation of ERK plays an important role in transcriptional activation of CD47 through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF inhibitor vemurafenib expressed higher levels of CD47...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537891/multiplex-pcr-approach-to-simultaneously-identify-several-mutations-in-fine-needle-cytology-thyroid-samples
#19
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
#20
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
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