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https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#1
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a  subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). Hoever, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
April 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/28346326/sarcomas-with-cic-rearrangements-are-a-distinct-pathologic-entity-with-aggressive-outcome-a-clinicopathologic-and-molecular-study-of-115-cases
#2
Cristina R Antonescu, Adepitan A Owosho, Lei Zhang, Sonja Chen, Kemal Deniz, Joseph M Huryn, Yu-Chien Kao, Shih-Chiang Huang, Samuel Singer, William Tap, Inga-Marie Schaefer, Christopher D Fletcher
CIC-DUX4 gene fusion, resulting from either a t(4;19) or t(10;19) translocation, is the most common genetic abnormality detected in EWSR1-negative small blue round cell tumors. Following their discovery it was debated if these tumors should be classified as variants of Ewing sarcoma (ie, atypical Ewing sarcoma) or as a stand-alone pathologic entity. As such the WHO classification temporarily grouped the CIC-rearranged tumors under undifferentiated sarcomas with round cell phenotype, until further clinical evidence was available...
March 24, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28337592/head-and-neck-round-cell-sarcomas-a-comparative-clinicopathologic-analysis-of-2-molecular-subsets-ewing-and-cic-rearranged-sarcomas
#3
Adepitan A Owosho, Cherry L Estilo, Joseph M Huryn, Lei Zhang, Christopher D M Fletcher, Cristina R Antonescu
CIC-rearranged sarcoma (CRS) is a relatively new entity defined by its pathognomonic genetic signature and undifferentiated round cell phenotype, initially grouped together with the 'Ewing sarcoma-like tumors'. However, increasing data suggest that these tumors should be regarded as a stand-alone pathologic entity. We conducted a clinicopathologic analysis on molecularly conformed Ewing sarcoma (ES) and CRS arising in the head and neck (HN) and compared to a well characterized cohort of ES and CRS from other locations...
March 23, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28296677/rbm10-tfe3-renal-cell-carcinoma-a-potential-diagnostic-pitfall-due-to-cryptic-intrachromosomal-xp11-2-inversion-resulting-in-false-negative-tfe3-fish
#4
MULTICENTER STUDY
Pedram Argani, Lei Zhang, Victor E Reuter, Satish K Tickoo, Cristina R Antonescu
Xp11 translocation renal cell carcinoma (RCC) are defined by chromosome translocations involving the Xp11 breakpoint which results in one of a variety of TFE3 gene fusions. TFE3 break-apart florescence in situ hybridization (FISH) assays are generally preferred to TFE3 immunohistochemistry (IHC) as a means of confirming the diagnosis in archival material, as FISH is less sensitive to the variable fixation which can result in false positive or false negative IHC. Prompted by a case report in the cytogenetics literature, we identify 3 cases of Xp11 translocation RCC characterized by a subtle chromosomal inversion involving the short arm of the X chromosome, resulting in an RBM10-TFE3 gene fusion...
May 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28291122/smarcb1-ini-1-deficient-sinonasal-carcinoma-a-series-of-39-cases-expanding-the-morphologic-and-clinicopathologic-spectrum-of-a-recently-described-entity
#5
Abbas Agaimy, Arndt Hartmann, Cristina R Antonescu, Simion I Chiosea, Samir K El-Mofty, Helene Geddert, Heinrich Iro, James S Lewis, Bruno Märkl, Stacey E Mills, Marc-Oliver Riener, Thomas Robertson, Ann Sandison, Sabine Semrau, Roderick H W Simpson, Edward Stelow, William H Westra, Justin A Bishop
To more fully characterize the clinical and pathologic spectrum of a recently described tumor entity of the sinonasal tract characterized by loss of nuclear expression of SMARCB1 (INI1), we analyzed 39 SMARCB1-deficient sinonasal carcinomas collected from multiple medical centers. The tumors affected 23 males and 16 females with an age range of 19 to 89 years (median, 52). All patients presented with locally advanced disease (T3, n=5; T4, n=27) involving the sinuses (mainly ethmoid) with variable involvement of the nasal cavity...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28270683/max-inactivation-is-an-early-event-in-gist-development-that-regulates-p16-and-cell-proliferation
#6
Inga-Marie Schaefer, Yuexiang Wang, Cher-Wei Liang, Nacef Bahri, Anna Quattrone, Leona Doyle, Adrian Mariño-Enríquez, Alexandra Lauria, Meijun Zhu, Maria Debiec-Rychter, Susanne Grunewald, Jaclyn F Hechtman, Armelle Dufresne, Cristina R Antonescu, Carol Beadling, Ewa T Sicinska, Matt van de Rijn, George D Demetri, Marc Ladanyi, Christopher L Corless, Michael C Heinrich, Chandrajit P Raut, Sebastian Bauer, Jonathan A Fletcher
KIT, PDGFRA, NF1 and SDH mutations are alternate initiating events, fostering hyperplasia in gastrointestinal stromal tumours (GISTs), and additional genetic alterations are required for progression to malignancy. The most frequent secondary alteration, demonstrated in ∼70% of GISTs, is chromosome 14q deletion. Here we report hemizygous or homozygous inactivating mutations of the chromosome 14q MAX gene in 16 of 76 GISTs (21%). We find MAX mutations in 17% and 50% of sporadic and NF1-syndromic GISTs, respectively, and we find loss of MAX protein expression in 48% and 90% of sporadic and NF1-syndromic GISTs, respectively, and in three of eight micro-GISTs, which are early GISTs...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28249647/a-clinicopathologic-study-on-ss18-fusion-positive-head-and-neck-synovial-sarcomas
#7
Adepitan A Owosho, Cherry L Estilo, Evan B Rosen, SaeHee K Yom, Joseph M Huryn, Cristina R Antonescu
OBJECTIVE: To determine clinicopathologic factors on survival in patients with head and neck synovial sarcoma. PATIENTS AND METHODS: We retrospectively identified patients with molecularly confirmed synovial sarcomas of the head and neck (SS-HN), either by the presence of SS18-SSX fusion transcript by RT-PCR or SS18 gene rearrangement by FISH, who were managed at our institution over a 20-year period (1996-2015). Kaplan-Meier survival analysis and log-rank test were performed to evaluate variables related to disease specific survival (DSS)...
March 2017: Oral Oncology
https://www.readbyqxmd.com/read/28248815/recurrent-srf-rela-fusions-define-a-novel-subset-of-cellular-myofibroma-myopericytoma-a-potential-diagnostic-pitfall-with-sarcomas-with-myogenic-differentiation
#8
Cristina R Antonescu, Yun-Shao Sung, Lei Zhang, Narasimhan P Agaram, Christopher D Fletcher
Cellular myofibroblastic tumors other than desmoid-type fibromatosis are often diagnostically challenging due to their relative rarity, lack of known genetic abnormalities, and expression of muscle markers which may be confused with sarcomas with myogenic differentiation. In this study we investigate the molecular alterations of a group of cellular myofibroblastic lesions with in the myofibroma and myopericytoma spectrum for better subclassification. Two index cases were studied by paired-end RNA sequencing for potential fusion gene discovery...
May 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#9
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28081303/the-novel-fusion-transcript-nr5a2-klhl29ft-is-generated-by-an-insertion-at-the-klhl29-locus
#10
Zhenguo Sun, Xiquan Ke, Steven L Salzberg, Daehwan Kim, Valentin Antonescu, Yulan Cheng, Binbin Huang, Jee Hoon Song, John M Abraham, Sariat Ibrahim, Hui Tian, Stephen J Meltzer
BACKGROUND: Novel fusion transcripts (FTs) caused by chromosomal rearrangement are common factors in the development of cancers. In the current study, the authors used massively parallel RNA sequencing to identify new FTs in colon cancers. METHODS: RNA sequencing (RNA-Seq) and TopHat-Fusion were used to identify new FTs in colon cancers. The authors then investigated whether the novel FT nuclear receptor subfamily 5, group A, member 2 (NR5A2)-Kelch-like family member 29 FT (KLHL29FT) was transcribed from a genomic chromosomal rearrangement...
May 1, 2017: Cancer
https://www.readbyqxmd.com/read/28035047/the-acyltransferase-lycat-controls-specific-phosphoinositides-and-related-membrane-traffic
#11
Leslie N Bone, Roya M Dayam, Minhyoung Lee, Nozomu Kono, Gregory D Fairn, Hiroyuki Arai, Roberto J Botelho, Costin N Antonescu
Phosphoinositides (PIPs) are key regulators of membrane traffic and signaling. The interconversion of PIPs by lipid kinases and phosphatases regulates their functionality. Phosphatidylinositol (PI) and PIPs have a unique enrichment of 1-stearoyl-2-arachidonyl acyl species; however, the regulation and function of this specific acyl profile remains poorly understood. We examined the role of the PI acyltransferase LYCAT in control of PIPs and PIP-dependent membrane traffic. LYCAT silencing selectively perturbed the levels and localization of phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol-3-phosphate and the membrane traffic dependent on these specific PIPs but was without effect on phosphatidylinositol-4-phosphate or biosynthetic membrane traffic...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28028572/romanian-medicine-european-medicine
#12
EDITORIAL
Ioan Cristian Stoica, Dinu Antonescu, Adrian Pana, Stefan Mogos, Romain Seil
The aim of the present paper is to present the message transmitted by the Presidential Lecture given during the first congress of arthroscopy organised in Romania, in March 2016, by the Romanian Society of Arthroscopy and Sports Trauma (SRATS). The goal was to present the evolution of medical care in Romania over the years, with the remarkable progress made in the first half of the twentieth century and the current status of arthroscopic surgery as seen from the point of view of medical professionals, as well as from a governmental point of view...
December 28, 2016: Knee Surgery, Sports Traumatology, Arthroscopy: Official Journal of the ESSKA
https://www.readbyqxmd.com/read/28009602/ewsr1-fusions-with-creb-family-transcription-factors-define-a-novel-myxoid-mesenchymal-tumor-with-predilection-for-intracranial-location
#13
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Chun-Liang Chen, Sumathi Vaiyapuri, Marc K Rosenblum, Cristina R Antonescu
Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28007774/combined-kit-and-ctla-4-blockade-in-patients-with-refractory-gist-and-other-advanced-sarcomas-a-phase-ib-study-of-dasatinib-plus-ipilimumab
#14
Sandra P D'Angelo, Alexander N Shoushtari, Mary Louise Keohan, Mark A Dickson, Mrinal M Gounder, Ping Chi, Jennifer K Loo, Leigh Gaffney, Lee Schneider, Zarine Patel, Joseph Patrick Erinjeri, Mark J Bluth, Ana Sjoberg, Howard Streicher, Naoko Takebe, Li-Xuan Qin, Cristina Antonescu, Ronald P DeMatteo, Richard D Carvajal, William D Tap
Purpose: A phase Ib study of dasatinib plus ipilimumab in patients with gastrointestinal stromal tumor (GIST) and other sarcomas was performed on the basis of preclinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic.Experimental Design: A standard 3 + 3 design was used to evaluate the safety, efficacy, and immune correlates of treatment. Dose escalation cohorts received ipilimumab 10 or 3 mg/kg every 3 weeks, followed by maintenance every 12 weeks with escalating doses of dasatinib (70 mg daily, 100 mg daily, or 70 mg twice daily)...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27914109/bcor-upregulation-in-a-poorly-differentiated-synovial-sarcoma-with-ss18l1-ssx1-fusion-a-pathologic-and-molecular-pitfall
#15
Yu-Chien Kao, Yun-Shao Sung, Lei Zhang, Samuel Kenan, Samuel Singer, William D Tap, David Swanson, Brendan C Dickson, Cristina R Antonescu
The diagnosis of poorly differentiated synovial sarcoma (PD-SS) may be challenging due to overlapping morphologic features with other undifferentiated round cell sarcomas (URCS). Particularly relevant is the histologic overlap and shared BCOR overexpression between a subset of SS and URCS with various BCOR genetic abnormalities. Here, we report a case of PD-SS lacking the canonical SS18-SSX gene fusion, but showing strong BCOR immunoreactivity and BCOR gene abnormalities by FISH, which were misinterpreted as a URCS with BCOR gene rearrangements...
December 3, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27859477/primary-cutaneous-adenoid-cystic-carcinoma-with-myb-aberrations-report-of-three-cases-and-comprehensive-review-of-the-literature
#16
Carlos N Prieto-Granada, Lei Zhang, Cristina R Antonescu, Jean M Henneberry, Jane L Messina
Adenoid cystic carcinoma (ACC) is a relatively rare slow-growing and often-aggressive epithelial-myoepithelial neoplasm that arises in multiple organs including the skin. The t(6;9) (q22-23;p23-24) translocation, resulting in a MYB-NFIB gene fusion has been found in ACCs from the salivary glands and other organs. Recently, MYB aberrations occurring in a subset (40%) of primary cutaneous ACC (PCACC) examples was described. Herein, we report three additional cases of PCACC harboring MYB aberrations. The tumors presented in three males aged 43, 81 and 55 years old and affected the extremities in the first two patients and the scalp in the third one...
February 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27757134/circulating-plasma-micro-rnas-in-patients-with-major-depressive-disorder-treated-with-antidepressants-a-pilot-study
#17
Virgil Radu Enatescu, Ion Papava, Ileana Enatescu, Mirela Antonescu, Andrei Anghel, Edward Seclaman, Ioan Ovidiu Sirbu, Catalin Marian
OBJECTIVE: Significant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants. METHODS: At the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done...
September 2016: Psychiatry Investigation
https://www.readbyqxmd.com/read/27689858/long-term-effect-of-chemotherapy-intensity-modulated-radiation-therapy-chemo-imrt-on-dentofacial-development-in-head-and-neck-rhabdomyosarcoma-patients
#18
Adepitan A Owosho, Paul Brady, Suzanne L Wolden, Leonard H Wexler, Cristina R Antonescu, Joseph M Huryn, Cherry L Estilo
Dentofacial developmental abnormalities have been reported in head and neck rhabdomyosarcoma (HNRMS) patients treated with conventional radiotherapy technique and chemotherapy. This current study investigates dentofacial long-term effects among HNRMS survivors managed with intensity-modulated radiotherapy (IMRT) and chemotherapy. In general, IMRT is a more effective 3D-conformal radiotherapy technique, which delivers high doses of radiation to the tumor target while minimizing doses received by the surrounding normal tissues...
September 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27688110/a-clinicopathologic-study-of-head-and-neck-rhabdomyosarcomas-showing-foxo1-fusion-positive-alveolar-and-myod1-mutant-sclerosing-are-associated-with-unfavorable-outcome
#19
Adepitan A Owosho, Shih-Chiang Huang, Sonja Chen, Shruti Kashikar, Cherry L Estilo, Suzanne L Wolden, Leonard H Wexler, Joseph M Huryn, Cristina R Antonescu
BACKGROUND: Based on their distinctive histologic and genetic features, the latest WHO classification of soft tissue tumors includes four pathologic variants of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell-sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS) using the latest pathologic and molecular criteria reflecting this new subclassification in a large cohort...
October 2016: Oral Oncology
https://www.readbyqxmd.com/read/27631520/novel-high-grade-endometrial-stromal-sarcoma-a-morphologic-mimicker-of-myxoid-leiomyosarcoma
#20
Lien N Hoang, Amandeep Aneja, Niamh Conlon, Deborah F Delair, Sumit Middha, Ryma Benayed, Martee L Hensley, Kay J Park, Travis J Hollmann, Meera R Hameed, Cristina R Antonescu, Robert A Soslow, Sarah Chiang
Endometrial stromal sarcomas (ESS) are often underpinned by recurrent chromosomal translocations resulting in the fusion of genes involved in epigenetic regulation. To date, only YWHAE-NUTM2 rearrangements are associated with distinctive high-grade morphology and aggressive clinical behavior. We identified 3 ESS morphologically mimicking myxoid leiomyosarcoma of the uterus and sought to describe their unique histopathologic features and identify genetic alterations using next-generation sequencing. All cases displayed predominantly spindled cells associated with abundant myxoid stroma and brisk mitotic activity...
January 2017: American Journal of Surgical Pathology
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