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https://www.readbyqxmd.com/read/28594149/myb-mybl1-mybl2-and-nfib-gene-alterations-and-myc-overexpression-in-salivary-gland-adenoid-cystic-carcinoma
#1
Kana Fujii, Takayuki Murase, Shintaro Beppu, Kosuke Saida, Hisashi Takino, Ayako Masaki, Kei Ijichi, Kimihide Kusafuka, Yoshiyuki Iida, Tetsuro Onitsuka, Yasushi Yatabe, Nobuhiro Hanai, Yasuhisa Hasegawa, Hiroshi Inagaki
AIMS: Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long-term prognosis is poor. In this study, we examined alterations of AdCC-associated genes, MYB, MYBL1, MYBL2, and NFIB, and their target molecules including MYC. The results were correlated to clinicopathological profile of the patients. METHODS AND RESULTS: Using paraffin tumor sections from 33 cases of salivary gland AdCC, we performed a detailed fluorescence in situ hybridization (FISH) analysis for gene splits and fusions of MYB, MYBL1, MYBL2, and NFIB...
June 8, 2017: Histopathology
https://www.readbyqxmd.com/read/28500913/myb-fusions-and-cd-markers-as-tools-for-authentication-and-purification-of-cancer-stem-cells-from-salivary-adenoid-cystic-carcinoma
#2
Alex Panaccione, Yi Zhang, Molly Ryan, Christopher A Moskaluk, Karen S Anderson, Wendell G Yarbrough, Sergey V Ivanov
Cancer stem cells (CSC) are considered the major cause of aggressive tumor behavior, recurrence, metastases, and resistance to radiation, making them an attractive therapeutic target. However, isolation of CSC from tumor tissue and their characterization are challenging due to uncertainty about their molecular markers and conditions for their propagation. Adenoid cystic carcinoma (ACC), which arises predominantly in the salivary glands, is a slow-growing but relentless tumor that frequently invades nerves and metastasizes...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28498281/myb-labeling-by-immunohistochemistry-is-more-sensitive-and-specific-for-breast-adenoid-cystic-carcinoma-than-myb-labeling-by-fish
#3
Justin S Poling, Raluca Yonescu, Andrea P Subhawong, Rajni Sharma, Pedram Argani, Yi Ning, Ashley Cimino-Mathews
Breast adenoid cystic carcinoma (ACC) is a primary breast carcinoma that, like salivary gland ACC, displays the t(6;9) translocation resulting in the MYB-NFIB gene fusion and immunopositivity for MYB by immunohistochemistry (IHC). However, it is not well established whether MYB immunoreactivity or rearrangement can be used to support a diagnosis of ACC in a malignant basaloid or benign cribriform breast lesion. Whole sections of primary breast ACC (n=11), collagenous spherulosis (CS; n=7), and microglandular adenosis (MGA; n=5) and tissue microarrays containing 16 basal-like, triple-negative breast carcinomas (TNBC) were labeled for MYB by IHC and underwent MYB fluorescence in situ hybridization using a break-apart probe...
May 11, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28210977/genetic-characterization-of-adenoid-cystic-carcinoma-of-the-minor-salivary-glands-a-potential-familial-occurrence-in-first-degree-relatives
#4
Hani Ibrahim Channir, Thomas van Overeem Hansen, Simon Andreasen, Christina Westmose Yde, Katalin Kiss, Birgitte Wittenborg Charabi
Adenoid cystic carcinoma (AdCC) is a malignant salivary gland tumor. To date, no cases of AdCC in first-degree relatives have been reported in the literature. We present a 50-year-old female (Case 1) and this patients' father (Case 2), both of whom were diagnosed with AdCC of the minor salivary glands. Histology of Case 1 demonstrated a tubulocribriform AdCC whereas Case 2 primarily was an AdCC of solid type. Both cases harbored the MYB-NFIB gene fusion as demonstrated by FISH and RNA-sequencing. After filtering and selection of putative deleterious variants, whole exome sequencing identified 18 germline variants in common between Case 1 and Case 2...
February 16, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28139061/immunohistochemical-and-molecular-profile-of-salivary-gland-cancer-in-children
#5
Laura D Locati, Paola Collini, Martina Imbimbo, Marta Barisella, Adele Testi, Lisa F Licitra, Thomas Löning, Katharina Tiemann, Pasquale Quattrone, Emanuela Bimbatti, Stefano Chiaravalli, Michela Casanova, Elena Tamborini, Roberto Carta, Patrizia Gasparini, Marco Guzzo, Maura Massimino, Andrea Ferrari
BACKGROUND: Pediatric salivary gland carcinomas (SGCs) are very rare. They differ from the adult SGCs in terms of epidemiologic and clinical behavior, being generally limited only to selected histotypes (e.g. low-grade mucoepidermoid [LG-MEC] and acinic cell cancer [AcCC]) and characterized by very good outcome. Our aim was to investigate therapeutic targets on a series of pediatric SGCs by immunohistochemical and molecular analysis. METHODS: A retrospective analysis was performed to search for cases of pediatric SGCs in the database of the Pediatric Oncology Unit at the Istituto Nazionale Tumori and in the Pathology database at the Gerhard-Seifert-Reference-Centre...
January 31, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27974718/c-myb-overexpression-in-cytology-smears-of-tracheobronchial-and-pulmonary-adenoid-cystic-carcinomas
#6
Archana George Vallonthaiel, Deepali Jain, Varsha Singh, Kavneet Kaur, Karan Madan, Vinay Kumar, Venkateswaran K Iyer, Mehar Chand Sharma
AIMS: Adenoid cystic carcinoma (AdCC) is a malignant epithelial neoplasm that occurs rarely in the lower respiratory tract (LRT). AdCC at various sites is associated with the novel fusion transcript MYB-NFIB, along with the overexpression of the Myb protein. The expression of the Myb protein in AdCC of the LRT has not been evaluated much. STUDY DESIGN: Cases of AdCC of the LRT diagnosed on cytology or histology were retrieved from our institutional archives. c-Myb expression was analyzed on immunocytochemistry/immunohistochemistry (ICC/IHC) and was correlated with clinicopathological parameters...
2017: Acta Cytologica
https://www.readbyqxmd.com/read/27859477/primary-cutaneous-adenoid-cystic-carcinoma-with-myb-aberrations-report-of-three-cases-and-comprehensive-review-of-the-literature
#7
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/27821319/a-phase-ii-study-of-sorafenib-in-recurrent-and-or-metastatic-salivary-gland-carcinomas-translational-analyses-and-clinical-impact
#8
L D Locati, F Perrone, B Cortelazzi, C Bergamini, P Bossi, E Civelli, C Morosi, S Lo Vullo, M Imbimbo, P Quattrone, G P Dagrada, R Granata, C Resteghini, A Mirabile, S Alfieri, E Orlandi, L Mariani, G Saibene, S Pilotti, L Licitra
BACKGROUND: Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and β, RET, KIT)...
November 4, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27662035/frequent-nfib-associated-gene-rearrangement-in-adenoid-cystic-carcinoma-of-the-vulva
#9
Deyin Xing, Salwa Bakhsh, Nataliya Melnyk, Christina Isacson, Julie Ho, David G Huntsman, C Blake Gilks, Brigitte M Ronnett, Hugo M Horlings
Adenoid cystic carcinoma is a rare malignant tumor that usually arises in the major and minor salivary glands and other locations containing secretory glands, including the lower female genital tract. Lower female genital tract carcinomas with adenoid cystic differentiation can be subclassified into 2 distinct groups based on the presence or absence of high-risk HPV. Cervical mixed carcinomas with some adenoid cystic differentiation are high-risk HPV-related but pure adenoid cystic carcinomas of vulvar and cervical origin appear to be unrelated to high-risk HPV...
September 22, 2016: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/27566443/a-phase-ii-study-of-axitinib-ag-013736-in-patients-with-incurable-adenoid-cystic-carcinoma
#10
A L Ho, L Dunn, E J Sherman, M G Fury, S S Baxi, R Chandramohan, S Dogan, L G T Morris, G D Cullen, S Haque, C S Sima, A Ni, C R Antonescu, N Katabi, D G Pfister
BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. PATIENTS AND METHODS: This is a minimax two-stage, phase II trial that enrolled patients with incurable ACC of any primary site...
October 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27533466/adenoid-cystic-carcinoma-emerging-role-of-translocations-and-gene-fusions
#11
REVIEW
Piotr T Wysocki, Evgeny Izumchenko, Juliet Meir, Patrick K Ha, David Sidransky, Mariana Brait
Adenoid cystic carcinoma (ACC), the second most common salivary gland malignancy, is notorious for poor prognosis, which reflects the propensity of ACC to progress to clinically advanced metastatic disease. Due to high long-term mortality and lack of effective systemic treatment, the slow-growing but aggressive ACC poses a particular challenge in head and neck oncology. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to the ACC development have been recognized...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27491809/genetic-events-in-the-progression-of-adenoid-cystic-carcinoma-of-the-breast-to-high-grade-triple-negative-breast-cancer
#12
Nicola Fusco, Felipe C Geyer, Maria R De Filippo, Luciano G Martelotto, Charlotte K Y Ng, Salvatore Piscuoglio, Elena Guerini-Rocco, Anne M Schultheis, Laetitia Fuhrmann, Lu Wang, Achim A Jungbluth, Kathleen A Burke, Raymond S Lim, Anne Vincent-Salomon, Masamichi Bamba, Suzuko Moritani, Sunil S Badve, Shu Ichihara, Ian O Ellis, Jorge S Reis-Filho, Britta Weigelt
Adenoid cystic carcinoma of the breast is a rare histological type of triple-negative breast cancer with an indolent clinical behavior, often driven by the MYB-NFIB fusion gene. Here we sought to define the repertoire of somatic genetic alterations in two adenoid cystic carcinomas associated with high-grade triple-negative breast cancer. The different components of each case were subjected to copy number profiling and massively parallel sequencing targeting all exons and selected regulatory and intronic regions of 488 genes...
November 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27213588/the-impact-of-the-myb-nfib-fusion-proto-oncogene-in-vivo
#13
Oliver R Mikse, Jeremy H Tchaicha, Esra A Akbay, Liang Chen, Roderick T Bronson, Peter S Hammerman, Kwok-Kin Wong
Recurrent fusion of the v-myb avian myelobastosis viral oncogene homolog (MYB) and nuclear factor I/B (NFIB) generates the MYB-NFIB transcription factor, which has been detected in a high percentage of individuals with adenoid cystic carcinoma (ACC). To understand the functional role of this fusion protein in carcinogenesis, we generated a conditional mutant transgenic mouse that expresses MYB-NFIB along with p53 mutation in tissues that give rise to ACC: mammary tissue, salivary glands, or systemically in the whole body...
May 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27185061/cutaneous-cylindroma-it-s-all-about-myb
#14
Gabriele Corda, Arturo Sala
Cutaneous cylindroma is a rare benign tumour that occasionally turns into malignant cylindrocarcinoma. The cancer can be sporadic or emerge in the context of Brooke-Spiegler syndrome (BSS), an inheritable condition characterized by mutation of the gene CYLD, encoding a tumour suppressor protein that controls the activity of the transcription factor NF-kB. Sporadic cylindromas present histological features shared with adenoid cystic carcinoma (ACC), a head and neck cancer originating from salivary or other exocrine glands...
August 2016: Journal of Pathology
https://www.readbyqxmd.com/read/26969893/overexpression-of-myb-drives-proliferation-of-cyld-defective-cylindroma-cells
#15
Neil Rajan, Mattias K Andersson, Naomi Sinclair, André Fehr, Kirsty Hodgson, Christopher J Lord, Dmitry V Kazakov, Tomas Vanecek, Alan Ashworth, Göran Stenman
Cutaneous cylindroma is an adnexal tumour with apocrine differentiation. A predisposition to multiple cylindromas is seen in patients with Brooke-Spiegler syndrome, who carry germline mutations in the tumour suppressor gene CYLD. Previous studies of inherited cylindromas have highlighted the frequent presence of bi-allelic truncating CYLD mutations as a recurrent driver mutation. We have previously shown that sporadic cylindromas express either MYB-NFIB fusion transcripts or show evidence of MYB activation in the absence of such fusions...
June 2016: Journal of Pathology
https://www.readbyqxmd.com/read/26888403/-research-progress-on-characteristic-myb-nfib-fusion-gene-in-adenoid-cystic-carcinoma
#16
Jie Ding, Jun Chen, Wei Li, Xiaofeng Huang
No abstract text is available yet for this article.
November 2015: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/26862087/whole-genome-sequencing-of-salivary-gland-adenoid-cystic-carcinoma
#17
Eleni M Rettig, C Conover Talbot, Mark Sausen, Sian Jones, Justin A Bishop, Laura D Wood, Collin Tokheim, Noushin Niknafs, Rachel Karchin, Elana J Fertig, Sarah J Wheelan, Luigi Marchionni, Michael Considine, Carole Fakhry, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Patrick K Ha, Nishant Agrawal
Adenoid cystic carcinomas (ACC) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole-genome sequencing and expression and pathway analyses. In addition to the well-described MYB-NFIB fusion that was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%)...
April 2016: Cancer Prevention Research
https://www.readbyqxmd.com/read/26851182/adenoid-cystic-carcinoma-can-be-driven-by-myb-or-mybl1-rearrangements-new-insights-into-myb-and-tumor-biology
#18
COMMENT
Thomas J Gonda, Robert G Ramsay
A majority of adenoid cystic carcinomas (AdCC)-rare tumors of the salivary gland and some other organs-have recently been found to be driven by chromosomal translocations resulting in MYB-NFIB fusions. Brayer and colleagues and Mitani and colleagues have now reported that AdCCs can alternatively be driven by similar rearrangements involving a second MYB family gene, MYBL1, and that these two drivers act in remarkably similar ways.
February 2016: Cancer Discovery
https://www.readbyqxmd.com/read/26631609/novel-mybl1-gene-rearrangements-with-recurrent-mybl1-nfib-fusions-in-salivary-adenoid-cystic-carcinomas-lacking-t-6-9-translocations
#19
Yoshitsugu Mitani, Bin Liu, Pulivarthi H Rao, Vishnupriya J Borra, Mark Zafereo, Randal S Weber, Merrill Kies, Guillermina Lozano, P Andrew Futreal, Carlos Caulin, Adel K El-Naggar
PURPOSE: Adenoid cystic carcinoma (ACC) is an indolent salivary gland malignancy, characterized by t(6;9) translocations and MYB-NFIB gene fusions in approximately 50% of the tumors. The genetic alterations underlying t(6;9)-negative and t(6;9)-positive/MYB-NFIB fusion-negative ACC remain unknown. To uncover the genetic alterations in ACC lacking the canonical translocation and fusion transcript and identify new abnormalities in translocation positive tumors. EXPERIMENTAL DESIGN: We performed whole-genome sequencing in 21 salivary ACCs and conducted targeted molecular analyses in a validation set (81 patients)...
February 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26359351/adenoid-cystic-carcinoma-current-therapy-and-potential-therapeutic-advances-based-on-genomic-profiling
#20
REVIEW
Young Kwang Chae, Su Yun Chung, Andrew A Davis, Benedito A Carneiro, Sunandana Chandra, Jason Kaplan, Aparna Kalyan, Francis J Giles
Adenoid cystic carcinoma (ACC) is a rare cancer with high potential for recurrence and metastasis. Efficacy of current treatment options, particularly for advanced disease, is very limited. Recent whole genome and exome sequencing has dramatically improved our understanding of ACC pathogenesis. A balanced translocation resulting in the MYB-NFIB fusion gene appears to be a fundamental signature of ACC. In addition, sequencing has identified a number of other driver genes mutated in downstream pathways common to other well-studied cancers...
November 10, 2015: Oncotarget
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