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JAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic Morphology.

Megan J Fitzpatrick, Lucas R Massoth, Chelsea Marcus, Jo-Anne Vergilio, Eric Severson, Daniel Duncan, Shakti H Ramkissoon, Robert P Hasserjian, Annette S Kim, Aliyah R Sohani, Erik A Williams, Valentina Nardi,

Peripheral T-cell lymphoma (PTCL) comprises a heterogenous group of rare mature T-cell neoplasms. While some PTCL subtypes are well-characterized by histology, immunophenotype, and recurrent molecular alterations, others remain incompletely defined. In particular, the distinction between CD30+ PTCL, not otherwise specified and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma can ... Read more >>

Am J Surg Pathol (The American journal of surgical pathology)
[2021, 45(7):895-904]

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Clinicopathologic and Genomic Characterization of PD-L1 Positive Urothelial Carcinomas.

Richard S P Huang, James Haberberger, Lukas Harries, Eric Severson, Daniel L Duncan, N Lynn Ferguson, Amanda Hemmerich, Claire Edgerly, Karthikeyan Murugesan, Jinpeng Xiao, Deborah McEwan, Oliver Holmes, Matthew Hiemenz, Jeffrey Venstrom, Julia A Elvin, James Creeden, Douglas I Lin, Jeffrey S Ross, Shakti H Ramkissoon,

<h4>Introduction</h4>Pembrolizumab was approved with an accompanying companion diagnostic (CDx) assay (PD-L1 DAKO 22C3) for urothelial carcinoma (UC). In this study, we further characterize the clinicopathologic and genomic features of UC that are programmed death-ligand 1 (PD-L1) positive.<h4>Materials and methods</h4>The cohort of this study consisted of a total of 528 consecutive ... Read more >>

Oncologist (The oncologist)
[2021, 26(5):375-382]

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Histiocytic and Dendritic Cell Sarcomas of Hematopoietic Origin Share Targetable Genomic Alterations Distinct from Follicular Dendritic Cell Sarcoma.

Lucas R Massoth, Yin P Hung, Judith A Ferry, Robert P Hasserjian, Valentina Nardi, G Petur Nielsen, Sam Sadigh, Vinayak Venkataraman, Martin Selig, Alison M Friedmann, Wesley Samore, Jonathan Keith Killian, Riza Milante, Joseph Giessinger, Kathleen Foley-Peres, Chelsea Marcus, Eric Severson, Daniel Duncan, Smruthy Sivakumar, Jeffrey S Ross, Vikram Desphande, Shakti H Ramkissoon, Jo-Anne Vergilio, Abner Louissaint, Lawrence R Zukerberg, Erik A Williams,

<h4>Background</h4>Histiocytic and dendritic cell neoplasms are a diverse group of tumors arising from monocytic or dendritic cell lineage. Whereas the genomic features for Langerhans cell histiocytosis and Erdheim-Chester disease have been well described, other less common and often aggressive tumors in this broad category remain poorly characterized, and comparison studies ... Read more >>

Oncologist (The oncologist)
[2021, :]

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Comprehensive genomic profiling of metastatic collecting duct carcinoma, renal medullary carcinoma, and clear cell renal cell carcinoma.

Gennady Bratslavsky, Stephanie Gleicher, Joseph M Jacob, Thomas H Sanford, Oleg Shapiro, Dimitra Bourboulia, Laurie M Gay, Julie Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Eric Allan Severson, Jonathan Keith Killian, Alexa Betzig Schrock, Jon H Chung, Vincent A Miller, Mehdi Mollapour, Jeffrey S Ross,

<h4>Introduction and objective</h4>Unlike clear cell renal cell carcinoma (CCRCC), collecting duct carcinoma (CDC) and renal medullary carcinoma (RMC) are rare tumors that progress rapidly and appear resistant to current systemic therapies. We queried comprehensive genomic profiling to uncover opportunities for targeted therapy and immunotherapy.<h4>Material and methods</h4>DNA was extracted from 40 ... Read more >>

Urol Oncol (Urologic oncology)
[2021, 39(6):367.e1-367.e5]

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Genomic Analysis of Circulating Tumor DNA in 3,334 Patients with Advanced Prostate Cancer Identifies Targetable BRCA Alterations and AR Resistance Mechanisms.

Hanna Tukachinsky, Russell W Madison, Jon H Chung, Ole V Gjoerup, Eric A Severson, Lucas Dennis, Bernard J Fendler, Samantha Morley, Lei Zhong, Ryon P Graf, Jeffrey S Ross, Brian M Alexander, Wassim Abida, Simon Chowdhury, Charles J Ryan, Karim Fizazi, Tony Golsorkhi, Simon P Watkins, Andrew Simmons, Andrea Loehr, Jeffrey M Venstrom, Geoffrey R Oxnard,

<h4>Purpose</h4>Comprehensive genomic profiling (CGP) is of increasing value for patients with metastatic castration-resistant prostate cancer (mCRPC). mCRPC tends to metastasize to bone, making tissue biopsies challenging to obtain. We hypothesized CGP of cell-free circulating tumor DNA (ctDNA) could offer a minimally invasive alternative to detect targetable genomic alterations (GA) that ... Read more >>

Clin Cancer Res (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2021, 27(11):3094-3105]

Cited: 1 time

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Clinicopathologic and genomic characterization of PD-L1-positive uterine cervical carcinoma.

Richard S P Huang, James Haberberger, Karthikeyan Murugesan, Natalie Danziger, Matthew Hiemenz, Eric Severson, Daniel L Duncan, Shakti H Ramkissoon, Jeffrey S Ross, Julia A Elvin, Douglas I Lin,

Positive program death-ligand 1 (PD-L1) immunohistochemistry (IHC) is an approved companion diagnostic guiding the use of immune checkpoint inhibitors in uterine cervical carcinoma (CXC). The clinical and genomic features of PD-L1-positive (PD-L1<sup>positive</sup>) CXC have not been previously described. We reviewed the clinicopathologic and molecular features of 647 CXC cases that ... Read more >>

Mod Pathol (Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc)
[2021, :]

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The Application of Next-generation Sequencing Tumor Molecular Profiling in the Diagnosis and Management of a Case of Acute Myelogenous Leukemia With MLL-PTD in a Pediatric Heart Transplant Recipient.

William C Woolbright, Victor Wong, Eric Severson, Dennis J Kuo,

A 6-year-old girl with a history of heart transplantation was diagnosed with myelodysplastic syndrome, which progressed to acute myelogenous leukemia. Comprehensive genomic profiling of her tumor discovered an MLL-PTD (partial tandem duplication) and she received chemotherapy and a hematopoietic stem cell transplant (HSCT). She subsequently relapsed and tumor molecular profiling ... Read more >>

J Pediatr Hematol Oncol (Journal of pediatric hematology/oncology)
[2021, 43(2):e246-e249]

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Predictive Biomarkers for Immune Checkpoint Inhibitors in Metastatic Breast Cancer.

Abirami Sivapiragasam, Prashanth Ashok Kumar, Ethan S Sokol, Lee A Albacker, Jonathan K Killian, Shakti H Ramkissoon, Richard S P Huang, Eric A Severson, Charlotte A Brown, Natalie Danziger, Kimberly McGregor, Jeffrey S Ross,

We examined a large dataset of female metastatic breast cancers (MBCs) profiled with comprehensive genomic profiling (CGP) to identify the prevalence and distribution of immunotherapy responsiveness-associated biomarkers. DNA was extracted from 3831 consecutive MBCs: 1237 (ER<sup>pos</sup> /HER2<sup>neg</sup> ), 1953 ER<sup>neg</sup> /HER2<sup>amp</sup> , and 641 triple-negative breast cancer (TNBC). CGP was ... Read more >>

Cancer Med (Cancer medicine)
[2021, 10(1):53-61]

Cited: 2 times

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Molecular profiling of mesonephric and mesonephric-like carcinomas of cervical, endometrial and ovarian origin.

Douglas I Lin, Nikunj Shah, Julie Y Tse, Jonathan K Killian, Amanda Hemmerich, Claire Edgerly, James Haberberger, Eric A Severson, Richard S P Huang, Shakti H Ramkissoon, Jo-Anne Vergilio, Jeffrey S Ross, Julia A Elvin,

Mesonephric carcinoma is a rare cancer that most often arises within the cervix, and less frequently, in the ovary and endometrium. A retrospective search of our CLIA-certified and CAP-accredited reference molecular laboratory database (Foundation Medicine, Inc.) identified 20 mesonephric or mesonephric-like, cervical (n = 10), endometrial (n = 5), ovarian (n = 4) or peri-bladder (n = 1) ... Read more >>

Gynecol Oncol Rep (Gynecologic oncology reports)
[2020, 34:100652]

Cited: 1 time

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A pan-cancer analysis of PD-L1 immunohistochemistry and gene amplification, tumor mutation burden and microsatellite instability in 48,782 cases.

Richard S P Huang, James Haberberger, Eric Severson, Daniel L Duncan, Amanda Hemmerich, Claire Edgerly, Naomi Lynn Ferguson, Erik Williams, Julia Elvin, Jo-Anne Vergilio, Jonathan Keith Killian, Douglas I Lin, Julie Tse, Matthew Hiemenz, Clarence Owens, Natalie Danziger, Priti S Hegde, Jeffrey Venstrom, Brian Alexander, Jeffrey S Ross, Shakti H Ramkissoon,

PD-L1 immunohistochemistry (IHC) currently has the most Food and Drug Administration (FDA) approvals as a companion diagnostic (CDx) for immunotherapies in specific tumor types; however, multiple other immunotherapy biomarkers exist. We performed this study to examine and report the prevalence of PD-L1 expression in a wide variety of tumor types ... Read more >>

Mod Pathol (Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc)
[2021, 34(2):252-263]

Cited: 4 times

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Genomic Profiling of Circulating Tumor DNA From Cerebrospinal Fluid to Guide Clinical Decision Making for Patients With Primary and Metastatic Brain Tumors.

Lori A Ramkissoon, Worthy Pegram, James Haberberger, Natalie Danziger, Glenn Lesser, Roy Strowd, Sonika Dahiya, Thomas J Cummings, Wenya Linda Bi, Malak Abedalthagafi, Pratheesh Sathyan, Kimberly McGregor, Prasanth Reddy, Eric Severson, Erik Williams, Douglas Lin, Claire Edgerly, Richard S P Huang, Amanda Hemmerich, James Creeden, Charlotte Brown, Jeffrey Venstrom, Priti Hegde, Jeffrey S Ross, Brian M Alexander, Julia Elvin, Shakti H Ramkissoon,

Despite advances in systemic therapies for solid tumors, the development of brain metastases remains a significant contributor to overall cancer mortality and requires improved methods for diagnosing and treating these lesions. Similarly, the prognosis for malignant primary brain tumors remains poor with little improvement in overall survival over the last ... Read more >>

Front Neurol (Frontiers in neurology)
[2020, 11:544680]

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Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial.

Amy Burd, Ross L Levine, Amy S Ruppert, Alice S Mims, Uma Borate, Eytan M Stein, Prapti Patel, Maria R Baer, Wendy Stock, Michael Deininger, William Blum, Gary Schiller, Rebecca Olin, Mark Litzow, James Foran, Tara L Lin, Brian Ball, Michael Boyiadzis, Elie Traer, Olatoyosi Odenike, Martha Arellano, Alison Walker, Vu H Duong, Tibor Kovacsovics, Robert Collins, Abigail B Shoben, Nyla A Heerema, Matthew C Foster, Jo-Anne Vergilio, Tim Brennan, Christine Vietz, Eric Severson, Molly Miller, Leonard Rosenberg, Sonja Marcus, Ashley Yocum, Timothy Chen, Mona Stefanos, Brian Druker, John C Byrd,

Acute myeloid leukemia (AML) is the most common diagnosed leukemia. In older adults, AML confers an adverse outcome<sup>1,2</sup>. AML originates from a dominant mutation, then acquires collaborative transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Currently, AML treatment is initiated rapidly, precluding the ability to consider the mutational profile ... Read more >>

Nat Med (Nature medicine)
[2020, 26(12):1852-1858]

Cited: 2 times

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Targetable BRAF and RAF1 Alterations in Advanced Pediatric Cancers.

Andrew Rankin, Adrienne Johnson, Alison Roos, Geoffrey Kannan, Jeffrey Knipstein, Nicholas Britt, Mark Rosenzweig, James Haberberger, Dean Pavlick, Eric Severson, Jo-Anne Vergilio, Rachel Squillace, Rachel Erlich, Pratheesh Sathyan, Stuart Cramer, David Kram, Jeffrey Ross, Vince Miller, Prasanth Reddy, Brian Alexander, Siraj M Ali, Shakti Ramkissoon,

RAF family protein kinases signal through the MAPK pathway to orchestrate cellular proliferation, survival, and transformation. Identifying BRAF alterations in pediatric cancers is critically important as therapeutic agents targeting BRAF or MEK may be incorporated into the clinical management of these patients. In this study, we performed comprehensive genomic profiling ... Read more >>

Oncologist (The oncologist)
[2021, 26(1):e153-e163]

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Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD-L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer.

Richard S P Huang, Xinyan Li, James Haberberger, Ethan Sokol, Eric Severson, Daniel L Duncan, Amanda Hemmerich, Claire Edgerly, Erik Williams, Julia Elvin, Jo-Anne Vergilio, Jonathan Keith Killian, Douglas Lin, Matthew Hiemenz, Jinpeng Xiao, Deborah McEwan, Oliver Holmes, Natalie Danziger, Rachel Erlich, Garrett Frampton, Michael B Cohen, Kimberly McGregor, Prasanth Reddy, Dawn Cardeiro, Rachel Anhorn, Jeffrey Venstrom, Brian Alexander, Charlotte Brown, Lajos Pusztai, Jeffrey S Ross, Shakti H Ramkissoon,

<h4>Background</h4>We examined the current biomarker landscape in breast cancer when programmed death-ligand 1 (PD-L1) testing is integrated with comprehensive genomic profiling (CGP).<h4>Material and methods</h4>We analyzed data from samples of 312 consecutive patients with breast carcinoma tested with both CGP and PD-L1 (SP142) immunohistochemistry (IHC) during routine clinical care. These samples ... Read more >>

Oncologist (The oncologist)
[2020, 25(11):943-953]

Cited: 2 times

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Molecular genetic changes in solid pseudopapillary neoplasms (SPN) of the pancreas.

Elisa Rodriguez-Matta, Amanda Hemmerich, Jason Starr, Kabir Mody, Eric A Severson, Gerardo Colon-Otero,

Acta Oncol (Acta oncologica (Stockholm, Sweden))
[2020, 59(9):1024-1027]

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Vulvar Squamous Cell Carcinoma: Comprehensive Genomic Profiling of HPV+ Versus HPV- Forms Reveals Distinct Sets of Potentially Actionable Molecular Targets.

Erik A Williams, Adrienne J Werth, Radwa Sharaf, Meagan Montesion, Ethan S Sokol, Dean C Pavlick, Molly McLaughlin-Drubin, Rachel Erlich, Helen Toma, Kevin Jon Williams, Jeff M Venstrom, Brian M Alexander, Nikunj Shah, Natalie Danziger, Amanda C Hemmerich, Eric A Severson, Jonathan Keith Killian, Douglas I Lin, Jeffrey S Ross, Julie Y Tse, Shakti H Ramkissoon, Mark C Mochel, Julia A Elvin,

<h4>Purpose</h4>Vulvar squamous cell carcinoma (vSCC) encompasses two predominant variants: one associated with detectable high-risk strains of human papillomavirus (hrHPV) and a second form often occurring in the context of chronic dermatitis in postmenopausal women. Genomic assessment of a large-scale cohort of patients with aggressive vSCC may identify distinct mutational signatures.<h4>Materials ... Read more >>

JCO Precis Oncol (JCO precision oncology)
[2020, 4:]

Cited: 2 times

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Identifying Opportunities and Challenges for Patients With Sarcoma as a Result of Comprehensive Genomic Profiling of Sarcoma Specimens.

Margaret A Hay, Eric A Severson, Vincent A Miller, David A Liebner, Jo-Anne Vergilio, Sherri Z Millis, James L Chen,

<h4>Purpose</h4>Comprehensive genomic profiling (CGP) of sarcomas is rapidly being integrated into routine clinical care to help refine diagnosis and prognosis and determine treatment. However, little is known about barriers to successful CGP or its clinical utility in sarcoma. We set out to determine whether CGP alters physician treatment decision-making, and ... Read more >>

JCO Precis Oncol (JCO precision oncology)
[2020, 4:]

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Pan-Cancer Landscape Analysis Reveals Recurrent KMT2A-MAML2 Gene Fusion in Aggressive Histologic Subtypes of Thymoma.

Lucas R Massoth, Yin P Hung, Dora Dias-Santagata, Maristela Onozato, Nikunj Shah, Eric Severson, Daniel Duncan, Brendan J Gillespie, Nathan F Williams, Jeffrey S Ross, Jo-Anne Vergilio, Shannon K Harkins, Krzysztof Glomski, Valentina Nardi, Lawrence R Zukerberg, Robert P Hasserjian, Abner Louissaint, Erik A Williams,

<h4>Purpose</h4>Thymomas are epithelial neoplasms that represent the most common thymic tumors in adults. These tumors have been shown to harbor a relatively low mutational burden. As a result, there is a lack of genetic alterations that may be used prognostically or targeted therapeutically for this disease. Here, we describe a ... Read more >>

JCO Precis Oncol (JCO precision oncology)
[2020, 4:]

Cited: 3 times

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Genomic profiling of BCOR-rearranged uterine sarcomas reveals novel gene fusion partners, frequent CDK4 amplification and CDKN2A loss.

Douglas I Lin, Amanda Hemmerich, Claire Edgerly, Daniel Duncan, Eric A Severson, Richard S P Huang, Shakti H Ramkissoon, Yamicia D Connor, Meghan Shea, Jonathan L Hecht, Siraj M Ali, Jo-Anne Vergilio, Jeffrey S Ross, Julia A Elvin,

OBJECTIVE:Genomic alterations of BCOR via ZC3H7B-BCOR fusion or BCOR internal tandem duplication (ITD) define a subset of endometrial stromal sarcoma (ESS). The goals of this study were to: 1) determine the molecular landscape of BCOR-rearranged ESS, 2) to identify novel BCOR fusion gene partners in ESS and their associated clinicopathological ... Read more >>

Gynecol Oncol (Gynecologic oncology)
[2020, 157(2):357-366]

Cited: 3 times

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Comparison Between Integrated Genomic DNA/RNA Profiling and Fluorescence In Situ Hybridization in the Detection of MYC, BCL-2, and BCL-6 Gene Rearrangements in Large B-Cell Lymphomas.

Daniel P Cassidy, Jennifer R Chapman, Rafael Lopez, Kyle White, Yao-Shan Fan, Carmen Casas, Eric A Severson, Francisco Vega,

<h4>Objectives</h4>To compare fluorescence in situ hybridization (FISH) and a commercially available sequencing assay for comprehensive genomic profiling (CGP) to determine the best approach to identify gene rearrangements (GRs) in large B-cell lymphomas (LBCLs).<h4>Methods</h4>Comparison of standard-of-care FISH assays (including a two-probe approach for MYC; break-apart and fusion probes) and an integrated ... Read more >>

Am J Clin Pathol (American journal of clinical pathology)
[2020, 153(3):353-359]

Cited: 1 time

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Comprehensive Assessment of Immuno-oncology Biomarkers in Adenocarcinoma, Urothelial Carcinoma, and Squamous-cell Carcinoma of the Bladder.

Andrea Necchi, Russell Madison, Daniele Raggi, Joseph M Jacob, Gennady Bratslavsky, Oleg Shapiro, Julia A Elvin, Jo-Anne Vergilio, Jonathan K Killian, Nhu Ngo, Shakti Ramkissoon, Eric Severson, Amanda C Hemmerich, Richard Huang, Siraj M Ali, Jon H Chung, Prasanth Reddy, Vincent A Miller, Alexa B Schrock, Laurie M Gay, Brian M Alexander, Petros Grivas, Jeffrey S Ross,

<h4>Background</h4>In patients with rare histologies of bladder cancer, including adenocarcinoma of the bladder (ACB) and squamous-cell carcinoma (SCC), there are limited standard therapy options, defining an unmet medical need.<h4>Objective</h4>In this comparative comprehensive genomic profiling (CGP) study, genomic alterations (GAs), and immuno-oncology (IO) biomarkers have been analyzed.<h4>Design, setting, and participants</h4>Within the ... Read more >>

Eur Urol (European urology)
[2020, 77(4):548-556]

Cited: 9 times

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A Case of CCDC6-RET Fusion Mutation in Adult Acute Lymphoblastic Leukemia (ALL), a Known Activating Mutation Reported in ALL.

Mateo Mejia Saldarriaga, Amir Steinberg, Eric A Severson, Adam Binder,

We report the case of a patient with B-Cell Acute Lymphoblastic Leukemia (ALL) who was found to harbor a gene fusion involving the <i>CCDC6</i> and <i>RET</i> genes. Although the <i>RET</i> mutations have been identified before in other malignancies, and it is thought to represent a driver mutation in these neoplasms, ... Read more >>

Front Oncol (Frontiers in oncology)
[2019, 9:1303]

Cited: 0 times

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Treatment of Pediatric Glioblastoma with Combination Olaparib and Temozolomide Demonstrates 2-Year Durable Response.

Andge Valiakhmetova, Sergey Gorelyshev, Alexander Konovalov, Yuri Trunin, Alexander Savateev, David E Kram, Eric Severson, Amanda Hemmerich, Claire Edgerly, Daniel Duncan, Nicholas Britt, Richard S P Huang, Julia Elvin, Vincent Miller, Jeffrey S Ross, Laurie Gay, Joshua McCorkle, Andrew Rankin, Rachel L Erlich, Yakov Chudnovsky, Shakti H Ramkissoon,

For pediatric patients with high-grade gliomas, standard-of-care treatment includes surgery, chemotherapy, and radiation therapy; however, most patients ultimately succumb to their disease. With advances in genomic characterization of pediatric high-grade gliomas, the use of targeted therapies in combination with current treatment modalities offer the potential to improve survival in this ... Read more >>

Oncologist (The oncologist)
[2020, 25(2):e198-e202]

Cited: 2 times

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SMARCA4 inactivation defines a subset of undifferentiated uterine sarcomas with rhabdoid and small cell features and germline mutation association.

Douglas I Lin, Justin M Allen, Jonathan L Hecht, Jonathan K Killian, Nhu T Ngo, Claire Edgerly, Eric A Severson, Siraj M Ali, Rachel L Erlich, Shakti H Ramkissoon, Jo-Anne Vergilio, Jeffrey S Ross, Julia A Elvin,

A rare subset of aggressive SMARCA4-deficient uterine sarcomas has been recently proposed, with only a limited number of cases having been previously described. Here, we identify 16 additional cases of SMARCA4-deficient uterine sarcoma from the database of a large, CLIA-certified and CAP-accredited, reference molecular laboratory, and we expand on their ... Read more >>

Mod Pathol (Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc)
[2019, 32(11):1675-1687]

Cited: 7 times

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Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma.

Celina Ang, Samuel J Klempner, Siraj M Ali, Russell Madison, Jeffrey S Ross, Eric A Severson, David Fabrizio, Aaron Goodman, Razelle Kurzrock, James Suh, Sherri Z Millis,

The clinical deployment of immune checkpoint inhibitors (ICIs) has created a tandem drive for the identification of biomarkers linked to benefit. Comprehensive genomic profiling was performed to evaluate the frequency of genomic biomarkers of ICI response in 755 patients with advanced hepatocellular carcinoma (HCC). Median age was 62 years' old, ... Read more >>

Oncotarget (Oncotarget)
[2019, 10(40):4018-4025]

Cited: 12 times

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