416 results on '"Joanne Xiu"'
Search Results
2. Comparative molecular profiling of pancreatic ductal adenocarcinoma of the head versus body and tail
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Maen Abdelrahim, Abdullah Esmail, Anup Kasi, Nestor F. Esnaola, Joanne Xiu, Yasmine Baca, and Benjamin A. Weinberg
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Pancreatic ductal adenocarcinoma (PDAC) of the head (H) and body/tail (B/T) differ in embryonic origin, cell composition, blood supply, lymphatic and venous drainage, and innervation. We aimed to compare the molecular and tumor immune microenvironment (TIME) profiles of PDAC of the H vs. B/T. A total of 3499 PDAC samples were analyzed via next-generation sequencing (NGS) of RNA (whole transcriptome, NovaSeq), DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing), and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Significance was determined as p values adjusted for multiple corrections (q) of 0.05). Expression analysis of immuno-oncology (IO)-related genes showed significantly higher expression of CTLA4 and PDCD1 in H (q
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- 2024
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3. Multi-omic profiling reveals discrepant immunogenic properties and a unique tumor microenvironment among melanoma brain metastases
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Gino K. In, Jennifer R. Ribeiro, Jun Yin, Joanne Xiu, Matias A. Bustos, Fumito Ito, Frances Chow, Gabriel Zada, Lindsay Hwang, April K. S. Salama, Soo J. Park, Justin C. Moser, Sourat Darabi, Evidio Domingo-Musibay, Maria L. Ascierto, Kim Margolin, Jose Lutzky, Geoffrey T. Gibney, Michael B. Atkins, Benjamin Izar, Dave S. B. Hoon, and Ari M. VanderWalde
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses to immune checkpoint therapies. Prior research suggests that MBM exhibit poor tumor immune responses and are enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of a large, real-world melanoma cohort. MBM exhibited lower interferon-gamma (IFNγ) scores and T cell-inflamed scores compared to primary cutaneous melanoma (PCM) or extracranial metastases (ECM), which was independent of tumor mutational burden. Among MBM, there were fewer computationally inferred immune cell infiltrates, which correlated with lower TNF and IL12B mRNA levels. Ingenuity pathway analysis (IPA) revealed suppression of inflammatory responses and dendritic cell maturation pathways. MBM also demonstrated a higher frequency of pathogenic PTEN mutations and angiogenic signaling. Oxidative phosphorylation (OXPHOS) was enriched in MBM and negatively correlated with NK cell and B cell-associated transcriptomic signatures. Modulating metabolic or angiogenic pathways in MBM may improve responses to immunotherapy in this difficult-to-treat patient subset.
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- 2023
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4. Pan-tumor survey of ROS1 fusions detected by next-generation RNA and whole transcriptome sequencing
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Misako Nagasaka, Shannon S. Zhang, Yasmine Baca, Joanne Xiu, Jorge Nieva, Ari Vanderwalde, Jeffrey J. Swensen, David Spetzler, Wolfgang Michael Korn, Luis E. Raez, Stephen V. Liu, and Sai-Hong Ignatius Ou
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c-ROS1 ,Receptor tyrosine kinase fusions ,Non-small cell lung cancer ,Breast cancer ,Pan-tumor analysis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Two ROS1 tyrosine kinase inhibitors have been approved for ROS1 fusion positive (ROS1+) non-small cell lung cancer (NSCLC) tumors. We performed a pan-tumor analysis of the incidence of ROS1 fusions to assess if more ROS1+ patients who could benefit from ROS1 TKIs could be identified. Methods A retrospective analysis of ROS1 positive solid malignancies identified by targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples performed at Caris Life Science (Phoenix, AZ). Results A total of 259 ROS1+ solid malignancies were identified from approximately 175,350 tumors that underwent next-generation sequencing (12% from targeted RNA sequencing [Archer]; 88% from whole transcriptome sequencing). ROS1+ NSCLC constituted 78.8% of the ROS1+ solid malignancies, follow by glioblastoma (GBM) (6.9%), and breast cancer (2.7%). The frequency of ROS1 fusion was approximately 0.47% among NSCLC, 0.29% for GBM, 0.04% of breast cancer. The mean tumor mutation burden for all ROS1+ tumors was 4.8 mutations/megabase. The distribution of PD-L1 (22C3) expression among all ROS1+ malignancies were 0% (18.6%), 1%-49% (29.4%), and ≥ 50% (60.3%) [for NSCLC: 0% (17.8%); 1–49% (27.7%); ≥ 50% (53.9%). The most common genetic co-alterations of ROS1+ NSCLC were TP53 (29.1%), SETD2 (7.3%), ARIAD1A (6.3%), and U2AF1 (5.6%). Conclusions ROS1+ NSCLC tumors constituted the majority of ROS1+ solid malignancies with four major fusion partners. Given that > 20% of ROS1+ solid tumors may benefit from ROS1 TKIs treatment, comprehensive genomic profiling should be performed on all solid tumors.
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- 2023
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5. PBRM1 mutations might render a subtype of biliary tract cancers sensitive to drugs targeting the DNA damage repair system
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Kai Zimmer, Florian Kocher, Gerold Untergasser, Brigitte Kircher, Arno Amann, Yasmine Baca, Joanne Xiu, W. Micheal Korn, Martin D. Berger, Heinz-Josef Lenz, Alberto Puccini, Elisa Fontana, Anthony F. Shields, John L. Marshall, Michael Hall, Wafik S. El-Deiry, David Hsiehchen, Teresa Macarulla, Josep Tabernero, Renate Pichler, Moh’d Khushman, Upender Manne, Emil Lou, Dominik Wolf, Viktorija Sokolova, Simon Schnaiter, Alain G. Zeimet, Pat Gulhati, Gerlig Widmann, and Andreas Seeber
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Polybromo-1 (PBRM1) loss of function mutations are present in a fraction of biliary tract cancers (BTCs). PBRM1, a subunit of the PBAF chromatin-remodeling complex, is involved in DNA damage repair. Herein, we aimed to decipher the molecular landscape of PBRM1 mutated (mut) BTCs and to define potential translational aspects. Totally, 1848 BTC samples were analyzed using next-generation DNA-sequencing and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). siRNA-mediated knockdown of PBRM1 was performed in the BTC cell line EGI1 to assess the therapeutic vulnerabilities of ATR and PARP inhibitors in vitro. PBRM1 mutations were identified in 8.1% (n = 150) of BTCs and were more prevalent in intrahepatic BTCs (9.9%) compared to gallbladder cancers (6.0%) or extrahepatic BTCs (4.5%). Higher rates of co-mutations in chromatin-remodeling genes (e.g., ARID1A 31% vs. 16%) and DNA damage repair genes (e.g., ATRX 4.4% vs. 0.3%) were detected in PBRM1-mutated (mut) vs. PBRM1-wildtype (wt) BTCs. No difference in real-world overall survival was observed between PBRM1-mut and PBRM1-wt patients (HR 1.043, 95% CI 0.821–1.325, p = 0.731). In vitro, experiments suggested that PARP ± ATR inhibitors induce synthetic lethality in the PBRM1 knockdown BTC model. Our findings served as the scientific rationale for PARP inhibition in a heavily pretreated PBRM1-mut BTC patient, which induced disease control. This study represents the largest and most extensive molecular profiling study of PBRM1-mut BTCs, which in vitro sensitizes to DNA damage repair inhibiting compounds. Our findings might serve as a rationale for future testing of PARP/ATR inhibitors in PBRM1-mut BTCs.
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- 2023
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6. Activity of pemetrexed in pre-clinical chordoma models and humans
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Santosh Kesari, Feng Wang, Tiffany Juarez, Shashaanka Ashili, C. Pawan K. Patro, Jose Carrillo, Minhdan Nguyen, Judy Truong, Joan Levy, Josh Sommer, Daniel M. Freed, Joanne Xiu, Yuki Takasumi, Eric Bouffet, and Jaya M. Gill
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Medicine ,Science - Abstract
Abstract Chordomas are rare slow growing tumors, arising from embryonic remnants of notochord with a close predilection for the axial skeleton. Recurrence is common and no effective standard medical therapy exists. Thymidylate synthase (TS), an intracellular enzyme, is a key rate-limiting enzyme of DNA biosynthesis and repair which is primarily active in proliferating and metabolically active cells. Eighty-four percent of chordoma samples had loss of TS expression which may predict response to anti-folates. Pemetrexed suppresses tumor growth by inhibiting enzymes involved in folate metabolism, resulting in decreased availability of thymidine which is necessary for DNA synthesis. Pemetrexed inhibited growth in a preclinical mouse xenograft model of human chordoma. We report three cases of metastatic chordoma that had been heavily treated previously with a variety of standard therapies with poor response. In two cases, pemetrexed was added and objective responses were observed on imaging with one patient on continuous treatment for > 2 years with continued shrinkage. One case demonstrated tumor growth after treatment with pemetrexed. The two cases which had a favorable response had a loss of TS expression, whereas the one case with progressive disease had TS present. These results demonstrate the activity of pemetrexed in recurrent chordoma and warrant a prospective clinical trial which is ongoing (NCT03955042).
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- 2023
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7. CCR5 and CCL5 gene expression in colorectal cancer: comprehensive profiling and clinical value
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Fang-Shu Ou, Emil Lou, Joanne Xiu, Hiroyuki Arai, Francesca Battaglin, Heinz-Josef Lenz, Richard M Goldberg, Anthony F Shields, Yasmine Baca, Philip A Philip, John L Marshall, W Michael Korn, Andreas Seeber, Natsuko Kawanishi, Jingyuan Wang, Shivani Soni, Wu Zhang, Shannon M Mumenthaler, Joshua Millstein, Priya Jayachandran, Federico Innocenti, Annika Lenz, Sandra Algaze, Taline Khoukaz, Evanthia Roussos Torres, Jim P Abraham, Benjamin A Weinberg, and Alan P Venook
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background The C-C motif chemokine receptor 5 (CCR5)/C-C motif chemokine ligand 5 (CCL5) axis plays a major role in colorectal cancer (CRC). We aimed to characterize the molecular features associated with CCR5/CCL5 expression in CRC and to determine whether CCR5/CCL5 levels could impact treatment outcomes.Methods 7604 CRCs tested with NextGen Sequencing on DNA and RNA were analyzed. Molecular features were evaluated according to CCR5 and CCL5 tumor gene expression quartiles. The impact on treatment outcomes was assessed in two cohorts, including 6341 real-world patients and 429 patients from the Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial.Results CCR5/CCL5 expression was higher in right-sided versus left-sided tumors, and positively associated with consensus molecular subtypes 1 and 4. Higher CCR5/CCL5 expression was associated with higher tumor mutational burden, deficiency in mismatch repair and programmed cell death ligand 1 (PD-L1) levels. Additionally, high CCR5/CCL5 were associated with higher immune cell infiltration in the tumor microenvironment (TME) of MMR proficient tumors. Ingenuity pathway analysis revealed upregulation of the programmed cell death protein 1 (PD-1)/PD-L1 cancer immunotherapy pathway, phosphatase and tensin homolog (PTEN) and peroxisome proliferator-activated receptors (PPAR) signaling, and cytotoxic T-lymphocyte antigen 4 (CTLA-4) signaling in cytotoxic T lymphocytes, whereas several inflammation-related pathways were downregulated. Low CCR5/CCL5 expression was associated with increased benefit from cetuximab-FOLFOX treatment in the CALGB/SWOG 80405 trial, where significant treatment interaction was observed with biologic agents and chemotherapy backbone.Conclusions Our data show a strong association between CCR5/CCL5 gene expression and distinct molecular features, gene expression profiles, TME cell infiltration, and treatment benefit in CRC. Targeting the CCR5/CCL5 axis may have clinical applications in selected CRC subgroups and may play a key role in developing and deploying strategies to modulate the immune TME for CRC treatment.
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- 2024
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8. Pan-tumor survey of RET fusions as detected by next-generation RNA sequencing identified RET fusion positive colorectal carcinoma as a unique molecular subset
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Misako Nagasaka, Danielle Brazel, Yasmine Baca, Joanne Xiu, Mohammed Najeeb Al-Hallak, Chul Kim, Jorge Nieva, Jeffrey J. Swensen, David Spetzler, Wolfgang Michael Korn, Mark A. Socinski, Luis E. Raez, Balazs Halmos, and Sai-Hong Ignatius Ou
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RET fusion ,Pan-tumor survey ,Next-generation sequencing ,RNA sequencing ,Selpercatinib ,Pralsetinib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: RET fusions are driver alterations in cancer and are most commonly found in non-small cell lung cancer and well-differentiated thyroid cancer. However, RET fusion have been reported in other solid tumors. Material and methods: A retrospective analysis of RET+ solid malignancies identified by targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples performed at Caris Life Science (Phoenix, AZ). Results: As of March 22, 2022, a total of 378 RET+ solid malignancies were identified in 15 different tumor types and carcinoma of unknown primary (CUP) that underwent next-generation RNA sequencing. RET+ NSCLC and RET+ thyroid cancer constituted 66.9% and 11.1% of the RET+ solid malignancies, respectively. RET+ colorectal adenocarcinoma and RET+ breast adenocarcinoma constituted 10.1% and 2.6%, respectively. The estimated frequency of RET fusions within specific tumor types were NSCLC 0.7%, thyroid cancer 3.1%, colorectal cancer 0.2% and breast cancer 0.1%. KIF5B (46.8%) was the most common fusion partner followed by CCDC6 (28.3%) and NCOA4 (13.8%) in RET+ solid tumors. KIF5B-RET was the dominant fusion variant in RET+ NSCLC, NCOA4-RET was the dominant variant in RET+ colorectal carcinoma, and CCDC6-RET was the dominant variant in thyroid cancer. The most common single gene alterations in RET+ tumors were TP53 (34.8%), RASA1 (14.3%) and ARIAD1A (11.6%). RET+ CRC had a high median TMB of 20.0 and were commonly MSI-H. Conclusions: RET fusions were identified in multiple tumor types. With a higher median TMB and commonly MSI-H, RET fusion positive CRC may be a unique molecular subset of CRC.
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- 2023
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9. Identification of actionable targets for breast cancer intervention using a diversity outbred mouse model
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Jennifer B. Jacob, Kuang-Chung Wei, Gerold Bepler, Joyce D. Reyes, Andi Cani, Lisa Polin, Kathryn White, Seongho Kim, Nerissa Viola, Julie McGrath, Anthony Guastella, CongCong Yin, Qing-Shen Mi, Benjamin L. Kidder, Kay-Uwe Wagner, Stuart Ratner, Victoria Phillips, Joanne Xiu, Prahlad Parajuli, and Wei-Zen Wei
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Molecular biology ,Cancer ,Genomics ,Transcriptomics ,Science - Abstract
Summary: HER2-targeted therapy has improved breast cancer survival, but treatment resistance and disease prevention remain major challenges. Genes that enable HER2/Neu oncogenesis are the next intervention targets. A bioinformatics discovery platform of HER2/Neu-expressing Diversity Outbred (DO) F1 Mice was established to identify cancer-enabling genes. Quantitative Trait Loci (QTL) associated with onset ages and growth rates of spontaneous mammary tumors were sought. Twenty-six genes in 3 QTL contain sequence variations unique to the genetic backgrounds that are linked to aggressive tumors and 21 genes are associated with human breast cancer survival. Concurrent identification of TSC22D3, a transcription factor, and its target gene LILRB4, a myeloid cell checkpoint receptor, suggests an immune axis for regulation, or intervention, of disease. We also investigated TIEG1 gene that impedes tumor immunity but suppresses tumor growth. Although not an actionable target, TIEG1 study revealed genetic regulation of tumor progression, forming the basis of the genetics-based discovery platform.
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- 2023
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10. Molecular differences between lymph nodes and distant metastases compared with primaries in colorectal cancer patients
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Alberto Puccini, Andreas Seeber, Joanne Xiu, Richard M. Goldberg, Davide Soldato, Axel Grothey, Anthony F. Shields, Mohamed E. Salem, Francesca Battaglin, Martin D. Berger, Wafik S. El-Deiry, Ryuma Tokunaga, Madiha Naseem, Wu Zhang, Sukeshi Patel Arora, Moh’d M. Khushman, Michael J. Hall, Philip A. Philip, John L. Marshall, W. Michael Korn, and Heinz-Josef Lenz
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Lymph nodes (LNs) and distant metastases can arise from independent subclones of the primary tumor. Herein, we characterized the molecular landscape and the differences between LNs, distant metastases and primary colorectal cancers (CRCs). Samples were analyzed using next generation sequencing (NGS, MiSeq on 47 genes, NextSeq on 592 genes) and immunohistochemistry. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. In total, 11,871 samples were examined, comprising primaries (N = 5862), distant (N = 5605) and LNs metastases (N = 404). The most frequently mutated genes in LNs were TP53 (72%), APC (61%), KRAS (39%), ARID1A (20%), PIK3CA (12%). LNs showed a higher mean TMB (13 mut/MB) vs distant metastases (9 mut/MB, p
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- 2021
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11. Characterization of MET Exon 14 Skipping Alterations (in NSCLC) and Identification of Potential Therapeutic Targets Using Whole Transcriptome Sequencing
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So Yeon Kim, MD, Jun Yin, MD, Stephen Bohlman, MD, PhD, Phillip Walker, PhD, Sanja Dacic, MD, PhD, Chul Kim, MD, Hina Khan, MD, Stephen V. Liu, MD, Patrick C. Ma, MD, Misako Nagasaka, MD, PhD, Karen L. Reckamp, MD, Jim Abraham, PhD, Dipesh Uprety, MD, Feng Wang, PhD, Joanne Xiu, PhD, Jian Zhang, PhD, Haiying Cheng, MD, PhD, and Balazs Halmos, MD
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METex14 ,Non–small cell lung cancer ,Whole transcriptome sequencing ,RNA expression ,MDM2 ,Immune signatures ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Genomic alterations in the juxtamembrane exon 14 splice sites in NSCLC lead to increased MET stability and oncogenesis. We present the largest cohort study of MET Exon 14 (METex14) using whole transcriptome sequencing. Methods: A total of 21,582 NSCLC tumor samples underwent complete genomic profiling with next-generation sequencing of DNA (592 Gene Panel, NextSeq, whole exome sequencing, NovaSeq) and RNA (NovaSeq, whole transcriptome sequencing). Clinicopathologic information including programmed death-ligand 1 and tumor mutational burden were collected and RNA expression for mutation subtypes and MET amplification were quantified. Immunogenic signatures and potential pathways of invasion were characterized using single-sample gene set enrichment analysis and mRNA gene signatures. Results: A total of 533tumors (2.47%) with METex14 were identified. The most common alterations were point mutations (49.5%) at donor splice sites. Most alterations translated to increased MET expression, with MET co-amplification resulting in synergistic increase in expression (q < 0.05). Common coalterations were amplifications of MDM2 (19.0% versus 1.8% wild-type [WT]), HMGA2 (13.2% versus 0.98% WT), and CDK4 (10.0% versus 1.5% WT) (q < 0.05). High programmed death-ligand 1 > 50% (52.5% versus 27.3% WT, q < 0.0001) and lower proportion of high tumor mutational burden (>10 mutations per megabase, 8.3% versus 36.7% WT, p < 0.0001) were associated with METex14, which were also enriched in both immunogenic signatures and immunosuppressive checkpoints. Pathways associated with METex14 included angiogenesis and apical junction pathways (q < 0.05). Conclusions: METex14 splicing alterations and MET co-amplification translated to higher and synergistic MET expression at the transcriptomic level. High frequencies of MDM2 and CDK4 co-amplifications and association with multiple immunosuppressive checkpoints and angiogenic pathways provide insight into potential actionable targets for combination strategies in METex14 NSCLC.
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- 2022
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12. Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
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Christopher Dardis, David Donner, Nader Sanai, Joanne Xiu, Sandeep Mittal, Sharon K. Michelhaugh, Manjari Pandey, Santosh Kesari, Amy B. Heimberger, Zoran Gatalica, Michael W. Korn, Ashley L. Sumrall, and Surasak Phuphanich
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Gliosarcoma ,Glioblastoma ,Molecular profiling ,Pan-cancer analysis ,Epithelial-to-mesenchymal transition ,Immuno-evasion ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. Methods Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. Results Potentially meaningful associations (p
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- 2021
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13. Pan-cancer analysis of RNA expression of ANGIOTENSIN-I-CONVERTING ENZYME 2 reveals high variability and possible impact on COVID-19 clinical outcomes
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Andrew Elliott, Michelle Saul, Jia Zeng, John L. Marshall, Edward S. Kim, Misako Nagasaka, Heinz-Josef Lenz, Lee Schwartzberg, David Spetzler, Jim Abraham, Joanne Xiu, Phillip Stafford, and W. Michael Korn
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Medicine ,Science - Abstract
Abstract Patients with cancer demonstrate particularly poor outcomes from COVID-19. To provide information essential for understanding the biologic underpinnings of this association, we analyzed whole-transcriptome RNA expression data obtained from a large cohort of cancer patients to characterize expression of ACE2, TMPRSS2, and other proteases that are involved in viral attachment to and entry into target cells. We find substantial variability of expression of these factors across tumor types and identify subpopulations expressing ACE2 at very high levels. In some tumor types, especially in gastrointestinal cancers, expression of ACE2 and TMPRSS2 is highly correlated. Furthermore, we found infiltration with T-cell and natural killer (NK) cell infiltration to be particularly pronounced in ACE2-high tumors. These findings suggest that subsets of cancer patients exist with gene expression profiles that may be associated with heightened susceptibility to SARS-CoV-2 infection, in whom malignant tumors function as viral reservoir and possibly promote the frequently detrimental hyper-immune response in patients infected with this virus.
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- 2021
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14. Transient commensal clonal interactions can drive tumor metastasis
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Suha Naffar-Abu Amara, Hendrik J. Kuiken, Laura M. Selfors, Timothy Butler, Marco L. Leung, Cheuk T. Leung, Elaine P. Kuhn, Teodora Kolarova, Carina Hage, Kripa Ganesh, Richard Panayiotou, Rosemary Foster, Bo R. Rueda, Athena Aktipis, Paul Spellman, Tan A. Ince, Joanne Xiu, Matthew Oberley, Zoran Gatalica, Nicholas Navin, Gordon B. Mills, Rodrick T. Bronson, and Joan S. Brugge
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Science - Abstract
Cooperative interactions among tumor cells may have important implications for metastasis. Here, the authors examined the spatio-temporal nature of interactions among clonal populations of ovarian carcinoma cells and found that transient interactions cells can promote metastases via commensal interactions.
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- 2020
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15. Evaluating the impact of age on immune checkpoint therapy biomarkers
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Rossin Erbe, Zheyu Wang, Sharon Wu, Joanne Xiu, Neeha Zaidi, Jennifer La, David Tuck, Nathanael Fillmore, Nicolas A. Giraldo, Michael Topper, Stephen Baylin, Marc Lippman, Claudine Isaacs, Reva Basho, Ilya Serebriiskii, Heinz-Josef Lenz, Igor Astsaturov, John Marshall, Josephine Taverna, Jerry Lee, Elizabeth M. Jaffee, Evanthia T. Roussos Torres, Ashani Weeraratna, Hariharan Easwaran, and Elana J. Fertig
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Biology (General) ,QH301-705.5 - Published
- 2021
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16. BRCA1/2 Reversion Mutations in Patients Treated with Poly ADP-Ribose Polymerase (PARP) Inhibitors or Platinum Agents
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Sourat Darabi, David R. Braxton, Joanne Xiu, Benedito A. Carneiro, Jeff Swensen, Emmanuel S. Antonarakis, Stephen V. Liu, Rana R. McKay, David Spetzler, Wafik S. El-Deiry, and Michael J. Demeure
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BRCA1/2 ,reversion mutations ,PARP inhibitors ,resistance mechanisms ,platinum-based therapy ,Medicine (General) ,R5-920 - Abstract
Background: Reversion mutations in BRCA1/2, resulting in restoration of the open reading frame, have been identified as a mechanism of resistance to platinum-based chemotherapy or PARP inhibition. We sought to explore the incidence of BRCA1/2 reversion mutations in different tumor types. Methods: We retrospectively analyzed molecular profiling results from primary and/or metastatic tumor samples submitted by multiple institutions. The samples underwent DNA and RNA sequencing at a CLIA/CAP-certified clinical lab. Reversion mutations were called only in patients whose available clinical records showed the use of PARP inhibitors or platinum agents prior to tumor profiling. Results: Reversion mutations were identified in 75 of 247,926 samples profiled across all tumor types. Among patients carrying pathogenic or likely pathogenic BRCA1/2 mutations, reversion mutations in BRCA1/2 genes were seen in ovarian cancer (OC) (30/3424), breast cancer (BC) (27/1460), endometrial cancer (4/564), pancreatic cancer (2/340), cholangiocarcinoma (2/178), prostate cancer (5/461), cervical cancer (1/117), cancer of unknown primary (1/244), bladder cancer (1/300), malignant pleural mesothelioma (1/10), and a neuroendocrine tumor of the prostate. We identified 22 reversion mutations in BRCA1 and 8 in BRCA2 in OC. In BC, we detected 6 reversion mutations in BRCA1 and 21 in BRCA2. We compared molecular profile results of 14 high-grade serous ovarian cancers (HGSOC) with reversion mutations against 87 control HGSOC with pathogenic BRCA1/2 mutations without reversion mutations. Tumors with reversion mutations trended to have had lower ER expression (25% vs. 64%, p = 0.024, q = 0.82) and higher KDM6A mutation rate (15% vs. 0, p = 0.016, q = 0.82). Conclusions: We present one of the largest datasets reporting reversion mutations in BRCA1/2 genes across various tumor types. These reversion mutations were rare; this may be because some patients may not have had repeat profiling post-treatment. Repeat tumor profiling at times of treatment resistance can help inform therapy selection in the refractory disease setting.
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- 2022
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17. Machine learning analysis using 77,044 genomic and transcriptomic profiles to accurately predict tumor type
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Jim Abraham, Amy B. Heimberger, John Marshall, Elisabeth Heath, Joseph Drabick, Anthony Helmstetter, Joanne Xiu, Daniel Magee, Phillip Stafford, Chadi Nabhan, Sourabh Antani, Curtis Johnston, Matthew Oberley, Wolfgang Michael Korn, and David Spetzler
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cancer of Unknown Primary (CUP) occurs in 3–5% of patients when standard histological diagnostic tests are unable to determine the origin of metastatic cancer. Typically, a CUP diagnosis is treated empirically and has very poor outcomes, with median overall survival less than one year. Gene expression profiling alone has been used to identify the tissue of origin but struggles with low neoplastic percentage in metastatic sites which is where identification is often most needed. MI GPSai, a Genomic Prevalence Score, uses DNA sequencing and whole transcriptome data coupled with machine learning to aid in the diagnosis of cancer. The algorithm trained on genomic data from 34,352 cases and genomic and transcriptomic data from 23,137 cases and was validated on 19,555 cases. MI GPSai predicted the tumor type in the labeled data set with an accuracy of over 94% on 93% of cases while deliberating amongst 21 possible categories of cancer. When also considering the second highest prediction, the accuracy increases to 97%. Additionally, MI GPSai rendered a prediction for 71.7% of CUP cases. Pathologist evaluation of discrepancies between submitted diagnosis and MI GPSai predictions resulted in change of diagnosis in 41.3% of the time. MI GPSai provides clinically meaningful information in a large proportion of CUP cases and inclusion of MI GPSai in clinical routine could improve diagnostic fidelity. Moreover, all genomic markers essential for therapy selection are assessed in this assay, maximizing the clinical utility for patients within a single test.
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- 2021
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18. Identification of Novel CDH1-NRG2α and F11R-NRG2α Fusions in NSCLC Plus Additional Novel NRG2α Fusions in Other Solid Tumors by Whole Transcriptome Sequencing
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Sai-Hong Ignatius Ou, MD, PhD, Joanne Xiu, PhD, Misako Nagasaka, MD, Bing Xia, MD, Shannon S. Zhang, MD, Qing Zhang, PhD, Jeffrey J. Swensen, PhD, David Spetzler, MS, PhD, MBA, Wolfgang Michael Korn, MD, Viola W. Zhu, MD, PhD, and Stephen V. Liu, MD
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NRG2 fusion ,CDH1-NRG2α ,F11R-NRG2α ,Whole transcriptome sequencing ,ligand-fusion- positive malignancies ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: A novel CD74-NRG2α fusion has recently been identified in NSCLC. We surveyed a large tumor database comprehensively profiled by whole transcriptome sequencing to investigate the incidence and distribution of NRG2 fusions among various solid tumors. Methods: Tumor samples submitted for clinical molecular profiling at Caris Life Sciences (Phoenix, AZ) that underwent whole transcriptome sequencing (NovaSeq [Illumina, San Diego, CA]) were retrospectively analyzed for NRG2 fusion events. All NRG2 fusions with sufficient reads (> three junctional reads spanning ≥ seven nucleotides) were identified for manual review, characterization of fusion class, intact functional domains, EGF-like domain isoforms, breakpoints, frame retention, and co-occurring alterations by next-generation sequencing (NextSeq [Illumina, San Diego, CA], 592 genes). Results: Seven inframe functional (containing the intact EGF-like domain) NRG2α fusions were identified, namely, the following: (1) NSCLC (two of 9600, 0.02%: CDH1-NRG2α [C11, N2], F11R-NRG2α [F1, N4]); (2) endometrial (two of 3060, 0.065%: CPM-NRG2α [C2, N2], OPA3-NRG2α [O1, N2]); (3) ovarian (one of 5030, 0.02%: SPON1-NRG2α [S6, N2]); (4) prostate (one of 1600, 0.063%: PLPP1-NRG2α [P1, N2]); and (5) carcinoma of unknown origin (one of 1400, 0.07%: CYSTM1-NRG2α [C2, N2]). No NRG2β fusions were identified. Both NSCLC samples contained the reciprocal NRG2 fusions (NRG2-CDH1, NRG2-F11R). Almost all inframe NRG2α fusions have no (N = 6, 85.7%) or low (N = 1, 14.3%) programmed death-ligand 1 expression. No additional known driver mutations were identified in these seven NRG2α fusion-positive tumor samples. Conclusions: Similar to NRG1 fusions, NRG2α fusions are recurrent and rare ligand-fusions in NSCLC and other multiple tumor types, especially gynecologic malignancies.
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- 2021
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19. 495 Basal cell carcinoma demonstrates a T-cell exclusion immune phenotype in contrast to other anti-PD-1 therapy responsive cutaneous malignancies
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Geoffrey Gibney, Ari VanderWalde, Joanne Xiu, Joseph Drabick, Gino In, Steven O’Day, Kelsey Poorman, and W Korn
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
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20. Prevalence of Phosphatidylinositol-3-Kinase (PI3K) Pathway Alterations and Co-alteration of Other Molecular Markers in Breast Cancer
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Katia Khoury, Antoinette R. Tan, Andrew Elliott, Joanne Xiu, Zoran Gatalica, Arielle L. Heeke, Claudine Isaacs, Paula R. Pohlmann, Lee S. Schwartzberg, Michael Simon, W. Michael Korn, Sandra M. Swain, and Filipa Lynce
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breast cancer ,molecular profiling ,PIK3CA-AKT1-PTEN pathway ,PI3K inhibitor ,PD-L1 ,CDH1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: PI3K/AKT signaling pathway is activated in breast cancer and associated with cell survival. We explored the prevalence of PI3K pathway alterations and co-expression with other markers in breast cancer subtypes.Methods: Samples of non-matched primary and metastatic breast cancer submitted to a CLIA-certified genomics laboratory were molecularly profiled to identify pathogenic or presumed pathogenic mutations in the PIK3CA-AKT1-PTEN pathway using next generation sequencing. Cases with loss of PTEN by IHC were also included. The frequency of co-alterations was examined, including DNA damage response pathways and markers of response to immuno-oncology agents.Results: Of 4,895 tumors profiled, 3,558 (72.7%) had at least one alteration in the PIK3CA-AKT1-PTEN pathway: 1,472 (30.1%) harbored a PIK3CA mutation, 174 (3.6%) an AKT1 mutation, 2,682 (54.8%) had PTEN alterations (PTEN mutation in 7.0% and/or PTEN loss by IHC in 51.4% of cases), 81 (1.7%) harbored a PIK3R1 mutation, and 4 (0.08%) a PIK3R2 mutation. Most of the cohort consisted of metastatic sites (n = 2974, 60.8%), with PIK3CA mutation frequency increased in metastatic (32.1%) compared to primary sites (26.9%), p < 0.001. Other PIK3CA mutations were identified in 388 (7.9%) specimens, classified as “off-label,” as they were not included in the FDA-approved companion test for PIK3CA mutations. Notable co-alterations included increased PD-L1 expression and high tumor mutational burden in PIK3CA-AKT1-PTEN mutated cohorts. Novel concurrent mutations were identified including CDH1 mutations.Conclusions: Findings from this cohort support further exploration of the clinical benefit of PI3K inhibitors for “off-label” PIK3CA mutations and combination strategies with potential clinical benefit for patients with breast cancer.
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- 2020
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21. Molecular profile of BRCA-mutated biliary tract cancers
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Michael Hall, Arno Amann, Joanne Xiu, Alberto Puccini, Francesca Battaglin, Heinz-Josef Lenz, Mohamed E Salem, Gilbert Spizzo, Richard M Goldberg, Axel Grothey, Anthony F Shields, Sukeshi Patel Arora, Yasmine Baca, Wafik S El-Deiry, Philip A Philip, Madiha Nassem, John L Marshall, Florian Kocher, Dominik Wolf, W Michael Korn, Andreas Seeber, and Moh’d Khushman
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction Prognosis of biliary tract cancers (BTC) remains dismal and novel treatment strategies are needed to improve survival. BRCA mutations are known to occur in BTC but their frequency and the molecular landscape in which they are observed in distinct sites of BTC remain unknown.Material and methods Tumour samples from 1292 patients with BTC, comprising intrahepatic cholangiocarcinoma (IHC, n=746), extrahepatic cholangiocarcinoma (EHC, n=189) and gallbladder cancer (GBC, n=353), were analysed using next-generation sequencing (NGS). Tumour mutational burden (TMB) was calculated based on somatic non-synonymous missense mutations. Determination of tumour mismatch repair (MMR) or microsatellite instability (MSI) status was done by fragment analysis, immunohistochemistry and the evaluation of known microsatellite loci by NGS. Programmed death ligand 1 expression was analysed using immunohistochemistry.Results Overall, BRCA mutations were detected in 3.6% (n=46) of samples (BRCA1: 0.6%, BRCA2: 3%) with no significant difference in frequency observed based on tumour site. In GBC and IHC, BRCA2 mutations (4.0% and 2.7%) were more frequent than BRCA1 (0.3% and 0.4%, p
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- 2020
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22. Correction to: Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling
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Christopher Dardis, David Donner, Nader Sanai, Joanne Xiu, Sandeep Mittal, Sharon K. Michelhaugh, Manjari Pandey, Santosh Kesari, Amy B. Heimberger, Zoran Gatalica, Michael W. Korn, Ashley L. Sumrall, and Surasak Phuphanich
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Neurology. Diseases of the nervous system ,RC346-429 - Published
- 2021
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23. Expression of Immuno-Oncologic Biomarkers Is Enriched in Colorectal Cancers and Other Solid Tumors Harboring the A59T Variant of KRAS
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Emil Lou, Joanne Xiu, Yasmine Baca, Andrew C. Nelson, Benjamin A. Weinberg, Muhammad Shaalan Beg, Mohamed E. Salem, Heinz-Josef Lenz, Philip Philip, Wafik S. El-Deiry, and W. Michael Korn
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colon cancer ,colorectal cancer ,molecular oncology ,oncogene ,KRAS ,A59T ,Cytology ,QH573-671 - Abstract
The molecular heterogeneity of KRAS is well established, with a pool of variants comprising >75% of all known mutations; this pool includes mutations in classic codons 12, 13, and 61, as well as 146 and 117. In addition, there are rare variants that are more frequently encountered clinically due to the advances in next-generation sequencing and more widespread implementation of All-RAS sequencing over the past five years. We have previously identified a missense variant of KRAS, A59T, in a patient with CRC that was associated with a response to an epidermal growth factor inhibitor when added to chemotherapy, supporting the hypothesis that distinct biochemical impacts of different KRAS mutations may produce varied responses to targeted therapy. In this study, we explored a large genomic database comprising 17,909 cases of CRC to determine the prevalence of the A59T mutation and characterized the concurrent genomic alterations associated with this variant in more detail, particularly in relation to the expanding set of potential predictive immuno-oncologic biomarkers. We identified 14 cases of A59 mutations in this dataset (0.08% prevalence). We evaluated the prevalence of high tumor mutation burden (TMB), positive PD-L1 expression, and microsatellite instability-high/mismatch repair-deficiency (MSI-H/dMMR) using both next generation sequencing (NGS) and immunohistochemistry (IHC). The genomic features of pertinent signaling pathways were also described, including RAS pathway, chromatin remodeling, DDR, hedgehog signaling, PI3K, receptor tyrosine kinases, signal transduction, TGF-beta, TP53, and WNT. We uncovered a high level of association of predictive markers of responsiveness to checkpoint inhibition and potentially other forms of immunotherapy, with nearly half of all cases harboring microsatellite instability as assessed using NGS. A59T was also detected in 11 additional cancer types, most prominently in cases of gynecologic or other gastrointestinal sites of origin. This study provides supportive evidence that A59T, and possibly other similarly rare KRAS variants, co-occur with predictive biomarkers of response to immunotherapy.
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- 2021
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24. Desmoplastic Small Round Blue Cell Tumor: A Review of Treatment and Potential Therapeutic Genomic Alterations
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Ajaz Bulbul, Bridget Noel Fahy, Joanne Xiu, Sadaf Rashad, Asrar Mustafa, Hatim Husain, and Andrea Hayes-Jordan
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Desmoplastic small round blue cell tumors (DSRCTs) originate from a cell with multilineage potential. A molecular hallmark of DSRCT is the EWS-WT1 reciprocal translocation. Ewing sarcoma and DSRCT are treated similarly due to similar oncogene activation pathways, and DSRCT has been represented in very limited numbers in sarcoma studies. Despite aggressive therapy, median survival ranges from 17 to 25 months, and 5-year survival rates remain around 15%, with higher survival reported among those undergoing removal of at least 90% of tumor in the absence of extraperitoneal metastasis. Almost 100% of these tumors contain t(11;22) (p13;q12) translocation, and it is likely that EWS-WT1 functions as a transcription factor possibly through WT1 targets. While there is no standard protocol for this aggressive disease, treatment usually includes the neoadjuvant HD P6 regimen (high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV) alternating with ifosfamide and etoposide (IE) chemotherapy combined with aggressively attempted R0 resection). We aimed to review the molecular characteristics of DSRCTs to explore therapeutic opportunities for this extremely rare and aggressive cancer type.
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- 2017
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25. Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
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Justin Hwang, Xiaolei Shi, Andrew Elliott, Taylor E. Arnoff, Julie McGrath, Joanne Xiu, Phillip Walker, Hannah E. Bergom, Abderrahman Day, Shihab Ahmed, Sydney Tape, Allison Makovec, Atef Ali, Rami M. Shaker, Eamon Toye, Rachel Passow, John R. Lozada, Jinhua Wang, Emil Lou, Kent W. Mouw, Benedito A. Carneiro, Elisabeth I. Heath, Rana R. McKay, W. Michael Korn, Chadi Nabhan, Charles J. Ryan, and Emmanuel S. Antonarakis
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Cancer Research ,Oncology - Abstract
Purpose: In patients with metastatic prostate cancer (mPC), ATM and BRCA2 mutations dictate differences in PARPi inhibitor response and other therapies. We interrogated the molecular features of ATM- and BRCA2-mutated mPC to explain the divergent clinical outcomes and inform future treatment decisions. Experimental design: We examined a novel set of 1,187 mPCs after excluding microsatellite-instable (MSI) tumors. We stratified these based on ATM (n = 88) or BRCA2 (n = 98) mutations. As control groups, mPCs with mutations in 12 other homologous recombination repair (HRR) genes were considered non-BRCA2/ATM HRR-deficient (HRDother, n = 193), whereas lack of any HRR mutations were considered HRR-proficient (HRP; n = 808). Gene expression analyses were performed using Limma. Real-world overall survival was determined from insurance claims data. Results: In noncastrate mPCs, only BRCA2-mutated mPCs exhibited worse clinical outcomes to AR-targeted therapies. In castrate mPCs, both ATM and BRCA2 mutations exhibited worse clinical outcomes to AR-targeted therapies. ATM-mutated mPCs had reduced TP53 mutations and harbored coamplification of 11q13 genes, including CCND1 and genes in the FGF family. BRCA2-mutated tumors showed elevated genomic loss-of-heterozygosity scores and were often tumor mutational burden high. BRCA2-mutated mPCs had upregulation of cell-cycle genes and were enriched in cell-cycle signaling programs. This was distinct from ATM-mutated tumors. Conclusions: Tumoral ATM and BRCA2 mutations are associated with differential clinical outcomes when patients are stratified by treatments, including hormonal or taxane therapies. ATM- and BRCA2-mutated tumors exhibited differences in co-occurring molecular features. These unique molecular features may inform therapeutic decisions and development of novel therapies.
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- 2023
26. Abstract P4-08-06: Clock Genes in Breast Cancer
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Priya Jayachandran, Yasmine Baca, Joanne Xiu, Yuanzhong Pan, Phil Walker, Francesca Battaglin, Hiroyuki Arai, Moh’d Khushman, Janice Lu, Darcy Spicer, Shannon Mumenthaler, Richard Goldberg, Benjamin Weinberg, Emil Lou, Michael Hall, Arielle L. Heeke, W. Michael Korn, Steve A. Kay, Heinz-Josef Lenz, and Evanthia T. Roussos Torres
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Cancer Research ,Oncology - Abstract
Background: Disruption of circadian processes has been linked to cancer initiation, progression, metastasis, resistance, and mortality. Clock proteins are an emerging target for therapy in breast cancer. Circadian rhythms are controlled by a network of transcription/translation feedback loops primarily driven by BMAL and CLOCK and the transcriptional repressors period (PER1-3) and cryptochrome (CRY1-2). We investigated the molecular and clinical associations of clock genes in breast cancer. Methods: A total of 9563 breast tumors underwent molecular profiling (Caris Life Sciences). Analyses included next-generation sequencing of DNA (592 genes-NextSeq, WES-NovaSeq) and RNA (NovaSeq). Clock gene Score (CS) was determined using expression of clock pathway gene Z scores (positives of BMAL, CLOCK and negatives of PER1/2 and CRY1/2) and then stratified into quartiles. xCell was used to quantify immune cell infiltration in the tumor microenvironment (TME). ER/PR was tested by IHC and HER2 was tested by either IHC or CISH. Significance was determined as P values adjusted for multiple comparison (Q) of < 0.05. Real-world survival information was obtained from insurance claims data and was calculated from either tissue collection to last contact or time on treatment (TOT); comparison was done by Kaplan-Meier test. Results: TNBC had the highest median CS score, while HR+/HER2- had the lowest CS (0.96 vs 0.26 q Citation Format: Priya Jayachandran, Yasmine Baca, Joanne Xiu, Yuanzhong Pan, Phil Walker, Francesca Battaglin, Hiroyuki Arai, Moh’d Khushman, Janice Lu, Darcy Spicer, Shannon Mumenthaler, Richard Goldberg, Benjamin Weinberg, Emil Lou, Michael Hall, Arielle L. Heeke, W. Michael Korn, Steve A. Kay, Heinz-Josef Lenz, Evanthia T. Roussos Torres. Clock Genes in Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-06.
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- 2023
27. Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study
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Jingyuan Wang, Joanne Xiu, Alex Farrell, Yasmine Baca, Hiroyuki Arai, Francesca Battaglin, Natsuko Kawanishi, Shivani Soni, Wu Zhang, Joshua Millstein, Anthony F Shields, Axel Grothey, Benjamin A Weinberg, John L Marshall, Emil Lou, Moh'd Khushman, Davendra P S Sohal, Michael J Hall, Tianshu Liu, Matthew Oberley, David Spetzler, W Michael Korn, Lin Shen, and Heinz-Josef Lenz
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Oncology - Published
- 2023
28. Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis
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Andrew M. Fleming, Benjamin W. Deschner, Forrest W. Williard, Justin A. Drake, Ari Vanderwalde, Joanne Xiu, Bradley G. Somer, Danny Yakoub, Miriam W. Tsao, Evan S. Glazer, Paxton V. Dickson, David Shibata, Philip A. Philip, Jimmy J. Hwang, Anthony F. Shields, John L. Marshall, W. Michael Korn, Heinz‐Josef Lenz, and Jeremiah L. Deneve
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Oncology ,Surgery ,General Medicine - Published
- 2023
29. Abstract P3-05-08: Prevalence and prognosis of ER-loss in advanced invasive lobular carcinoma
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Whitney L. Hensing, Joanne Xiu, W. Michael Korn, Stephanie L. Graff, Irene Kang, Evanthia T. Roussos Torres, Arielle L. Heeke, Andrew A. Davis, Nusayba A. Bagegni, Katherine K. Clifton, Ron Bose, Cynthia Ma, and Foluso O. Ademuyiwa
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Cancer Research ,Oncology - Abstract
Introduction: Estrogen receptor (ER) loss occurs in about 20% of recurrent breast cancers (BC) and is associated with unresponsiveness to endocrine therapy (ET) and poor prognosis. Prior studies evaluating ER-loss included predominately patients with invasive ductal carcinoma (IDC), and therefore the impact of ER-loss in invasive lobular carcinoma (ILC) is unknown. In this retrospective analysis, using real-world data, we aimed to determine the prevalence and clinical significance of ER-loss in ILC. Methods: Advanced BC were molecularly profiled at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (592-gene panel or whole-exome sequencing), RNA (whole transcriptome sequencing, WTS) and immunohistochemistry (IHC) of select markers. A large real-world evidence (RWE) database combining Caris’ molecular data with clinical information obtained from insurance claims data (CODEai) was interrogated and overall survival (OS) was calculated from time of tissue collection to last patient contact. A tumor was considered to have ER-loss if therapies approved only for ER-positive BC were prescribed prior to obtaining a negative ER IHC result. OS was compared using Kaplan-Meier estimates for defined patient cohorts; significance was determined as p values < 0.05. For molecular analyses, Fisher-Exact or Chi-Square tests were used to determine p values. Correction for multiple comparisons was performed using Benjamini-Hochberg to calculate q values. Results: The RWE database included 24,824 patients with advanced BC. At the time of tissue collection for molecular profiling, 6,786 advanced BC patients had been previously treated with ET (with or without mTOR or CDK4/6 inhibitors), of whom 1,338 had data available on histologic classification and ER IHC. The final analytical cohort included 263 patients with ILC and 1,075 with IDC. ER-loss was identified in 11.4% of ILC (n=30/263) and 19.6% (n=210/1075) of IDC (p=0.0017). In ILC, ER-loss was associated with significantly worse OS (HR: 1.75, 95%CI: 1.10-2.79, p=0.016) compared with no ER-loss. In the cohort of patients with ER-loss, patients with ILC had significantly worse OS compared with IDC (HR=2.03, 95% CI: 1.267-3.251, p=0.003). Further, when 1,016 tumors with ER-loss (regardless of histology) were stratified by the median OS (mOS=11mo), positive PD-L1 expression (34% vs. 22%, p=0.04, q=0.22), HER2 IHC positivity (16% vs. 7.8%, p=0.003, q=0.08) and HER2 amplification (16% vs. 4.7%, p=0.0006, q=0.04) were enriched in patients with longer mOS; while amplification of TEFB (0.38% vs. 2.6%, p=0.047, q=0.23) and MYB (0.38% vs. 2.6%, p=0.047, q=0.23) were enriched in patients with shorter mOS. WTS identified 197 differentially expressed genes, the majority of which were enriched in patients with longer mOS (q< 0.05). Conclusions: In this large real-word dataset, ER-loss likely occurred in 11.4% of ILC and was associated with worse OS compared to both patients with IDC and ER-loss and ILC without ER-loss. Our analysis had several limitations; notably, our definition of ER-loss was based on prior treatment, we could not distinguish between de novo or recurrent metastatic disease and time of tissue collection was not standardized during the course of treatment. Thus, additional studies are needed to confirm these findings. However, this study does suggest that ER-loss occurs in a subset of patients with ILC and has poor prognostic implications. Citation Format: Whitney L. Hensing, Joanne Xiu, W. Michael Korn, Stephanie L. Graff, Irene Kang, Evanthia T. Roussos Torres, Arielle L. Heeke, Andrew A. Davis, Nusayba A. Bagegni, Katherine K. Clifton, Ron Bose, Cynthia Ma, Foluso O. Ademuyiwa. Prevalence and prognosis of ER-loss in advanced invasive lobular carcinoma [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-08.
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- 2023
30. Supplementary Figure 2 from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
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Emmanuel S. Antonarakis, Charles J. Ryan, Chadi Nabhan, W. Michael Korn, Rana R. McKay, Elisabeth I. Heath, Benedito A. Carneiro, Kent W. Mouw, Emil Lou, Jinhua Wang, John R. Lozada, Rachel Passow, Eamon Toye, Rami M. Shaker, Atef Ali, Allison Makovec, Sydney Tape, Shihab Ahmed, Abderrahman Day, Hannah E. Bergom, Phillip Walker, Joanne Xiu, Julie McGrath, Taylor E. Arnoff, Andrew Elliott, Xiaolei Shi, and Justin Hwang
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Tumor mutation burden (muts/Mb) of ATM and BRCA2 mutant mPCs.
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- 2023
31. Supplementary Table 3 from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
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Emmanuel S. Antonarakis, Charles J. Ryan, Chadi Nabhan, W. Michael Korn, Rana R. McKay, Elisabeth I. Heath, Benedito A. Carneiro, Kent W. Mouw, Emil Lou, Jinhua Wang, John R. Lozada, Rachel Passow, Eamon Toye, Rami M. Shaker, Atef Ali, Allison Makovec, Sydney Tape, Shihab Ahmed, Abderrahman Day, Hannah E. Bergom, Phillip Walker, Joanne Xiu, Julie McGrath, Taylor E. Arnoff, Andrew Elliott, Xiaolei Shi, and Justin Hwang
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Comparisons of WTS profiles between ATMm and BRCA2m to the HRP group.
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- 2023
32. Supplementary Figure 3 from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
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Emmanuel S. Antonarakis, Charles J. Ryan, Chadi Nabhan, W. Michael Korn, Rana R. McKay, Elisabeth I. Heath, Benedito A. Carneiro, Kent W. Mouw, Emil Lou, Jinhua Wang, John R. Lozada, Rachel Passow, Eamon Toye, Rami M. Shaker, Atef Ali, Allison Makovec, Sydney Tape, Shihab Ahmed, Abderrahman Day, Hannah E. Bergom, Phillip Walker, Joanne Xiu, Julie McGrath, Taylor E. Arnoff, Andrew Elliott, Xiaolei Shi, and Justin Hwang
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AR activities and NEPC signatures in ATM- and BRCA2- mutated tumors.
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- 2023
33. Supplementary Figure 1 from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
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Emmanuel S. Antonarakis, Charles J. Ryan, Chadi Nabhan, W. Michael Korn, Rana R. McKay, Elisabeth I. Heath, Benedito A. Carneiro, Kent W. Mouw, Emil Lou, Jinhua Wang, John R. Lozada, Rachel Passow, Eamon Toye, Rami M. Shaker, Atef Ali, Allison Makovec, Sydney Tape, Shihab Ahmed, Abderrahman Day, Hannah E. Bergom, Phillip Walker, Joanne Xiu, Julie McGrath, Taylor E. Arnoff, Andrew Elliott, Xiaolei Shi, and Justin Hwang
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Overall survival of ATM, BRCA2 mutant, and HRDother mPCs.
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- 2023
34. Supplementary Table 1 from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
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Emmanuel S. Antonarakis, Charles J. Ryan, Chadi Nabhan, W. Michael Korn, Rana R. McKay, Elisabeth I. Heath, Benedito A. Carneiro, Kent W. Mouw, Emil Lou, Jinhua Wang, John R. Lozada, Rachel Passow, Eamon Toye, Rami M. Shaker, Atef Ali, Allison Makovec, Sydney Tape, Shihab Ahmed, Abderrahman Day, Hannah E. Bergom, Phillip Walker, Joanne Xiu, Julie McGrath, Taylor E. Arnoff, Andrew Elliott, Xiaolei Shi, and Justin Hwang
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Composition and rates of all detectable genomic features detectable through the Caris diagnostic platform.
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- 2023
35. Data from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
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Emmanuel S. Antonarakis, Charles J. Ryan, Chadi Nabhan, W. Michael Korn, Rana R. McKay, Elisabeth I. Heath, Benedito A. Carneiro, Kent W. Mouw, Emil Lou, Jinhua Wang, John R. Lozada, Rachel Passow, Eamon Toye, Rami M. Shaker, Atef Ali, Allison Makovec, Sydney Tape, Shihab Ahmed, Abderrahman Day, Hannah E. Bergom, Phillip Walker, Joanne Xiu, Julie McGrath, Taylor E. Arnoff, Andrew Elliott, Xiaolei Shi, and Justin Hwang
- Abstract
Purpose:In patients with metastatic prostate cancer (mPC), ATM and BRCA2 mutations dictate differences in PARPi inhibitor response and other therapies. We interrogated the molecular features of ATM- and BRCA2-mutated mPC to explain the divergent clinical outcomes and inform future treatment decisions.Experimental design:We examined a novel set of 1,187 mPCs after excluding microsatellite-instable (MSI) tumors. We stratified these based on ATM (n = 88) or BRCA2 (n = 98) mutations. As control groups, mPCs with mutations in 12 other homologous recombination repair (HRR) genes were considered non-BRCA2/ATM HRR-deficient (HRDother, n = 193), whereas lack of any HRR mutations were considered HRR-proficient (HRP; n = 808). Gene expression analyses were performed using Limma. Real-world overall survival was determined from insurance claims data.Results:In noncastrate mPCs, only BRCA2-mutated mPCs exhibited worse clinical outcomes to AR-targeted therapies. In castrate mPCs, both ATM and BRCA2 mutations exhibited worse clinical outcomes to AR-targeted therapies. ATM-mutated mPCs had reduced TP53 mutations and harbored coamplification of 11q13 genes, including CCND1 and genes in the FGF family. BRCA2-mutated tumors showed elevated genomic loss-of-heterozygosity scores and were often tumor mutational burden high. BRCA2-mutated mPCs had upregulation of cell-cycle genes and were enriched in cell-cycle signaling programs. This was distinct from ATM-mutated tumors.Conclusions:Tumoral ATM and BRCA2 mutations are associated with differential clinical outcomes when patients are stratified by treatments, including hormonal or taxane therapies. ATM- and BRCA2-mutated tumors exhibited differences in co-occurring molecular features. These unique molecular features may inform therapeutic decisions and development of novel therapies.
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- 2023
36. The Genomic Landscape of Vulvar Squamous Cell Carcinoma
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Logan Corey, John J. Wallbillich, Sharon Wu, Alex Farrell, Kurt Hodges, Joanne Xiu, Chadi Nabhan, Anthony Guastella, Mira Kheil, Radhika Gogoi, Ira Winer, Sudeshna Bandyopadhyay, Marilyn Huang, Nathaniel Jones, Annelise Wilhite, Anthony Karnezis, Premal Thaker, Thomas J. Herzog, Matthew Oberley, William Michael Korn, Alex Vezina, Robert Morris, and Rouba Ali-Fehmi
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Obstetrics and Gynecology ,Pathology and Forensic Medicine - Published
- 2023
37. Molecular profiles of endometrial cancer tumors among Black patients
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Annelise M, Wilhite, Yasmine, Baca, Joanne, Xiu, Rajesh, Paladugu, Adam C, ElNaggar, Jubilee, Brown, Ira S, Winer, Robert, Morris, Britt K, Erickson, Alexander B, Olawaiye, Matthew, Powell, W Michael, Korn, Rodney P, Rocconi, Dineo, Khabele, and Nathaniel L, Jones
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Carcinosarcoma ,Oncology ,Mutation ,Black People ,Humans ,Obstetrics and Gynecology ,Female ,Microsatellite Instability ,Carcinoma, Endometrioid ,Endometrial Neoplasms - Abstract
Disparate outcomes exist between Black and White patients with endometrial cancer (EC). One contributing factor is the disproportionately low representation of Black patients in clinical trials and in tumor molecular profiling studies. Our objective was to investigate molecular profiles of ECs in a cohort with a high proportion of tumors from Black patients.A total of 248 EC samples and self-reported race data were collected from 6 institutions. Comprehensive tumor profiling and analyses were performed by Caris Life Sciences.Tumors from 105 (42%) Black and 143 (58%) White patients were included. Serous histology (58% vs 36%) and carcinosarcoma (25% vs 16%), was more common among Black patients, and endometrioid was less common (17% vs 48%) (p0.01). Differences in gene mutations between cohorts corresponded to observed histologic differences between races. Specifically, TP53 mutations were predominant in serous tumors. In endometrioid tumors, mutations in ARID1A were the most common, and high rates of MSI-H, MMRd, and TMB-H were observed. In carcinosarcoma tumors, hormone receptor expression was high in tumors of Black patients (PR 23.4%, ER 30.8%). When stratified by histology, there were no significant differences between tumors from Black and White women.This cohort had a high proportion of tumors from Black women. Distinct molecular profiles were driven primarily by more aggressive histologic subtypes among Black women. Continued effort is needed to include Black women and other populations under-represented in EC molecular profiling studies as targeted therapies and personalized medicine become mainstream.
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- 2022
38. Capicua (CIC) mutations in gliomas in association with MAPK activation for exposing a potential therapeutic target
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Sourat Darabi, Joanne Xiu, Timothy Samec, Santosh Kesari, Jose Carrillo, Sonikpreet Aulakh, Kyle M. Walsh, Soma Sengupta, Ashley Sumrall, David Spetzler, Michael Glantz, and Michael J Demeure
- Abstract
Gliomas are the most prevalent neurological cancer in the United States and care modalities are not able to effectively combat these aggressive malignancies. Identifying new, more effective treatments require a deep understanding of the complex genetic variations and relevant pathway associations behind these cancers. Drawing connections between gene mutations with a responsive genetic target can help drive therapy selections to enhance patient survival. We have performed extensive molecular profiling of the Capicua gene (CIC), a tumor and transcriptional suppressor gene, and its mutation prevalence in reference to MAPK activation within clinical glioma tissue. CIC mutations occur far more frequently in oligodendroglioma (52.1%) than in low-grade astrocytoma or glioblastoma. CIC-associated mutations were observed across all glioma subtypes, and MAPK-associated mutations were most prevalent in CIC wild-type tissue regardless of the glioma subtype. MAPK activation, however, was enhanced in CIC-mutated oligodendroglioma. The totality of our observations reported supports the use of CIC as a relevant genetic marker for MAPK activation. Identification of CIC mutations, or lack thereof, can assist in selecting, implementing, and developing MEK/MAPK-inhibitory trials to improve patient outcomes potentially.
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- 2023
39. Supplemental Figure 1 from Association of Homologous Recombination–DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers
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Sunnie S. Kim, Jia Zeng, Richard M. Goldberg, Philip A. Philip, Mohamed Salem, W. Michael Korn, Heinz-Josef Lenz, Anthony F. Shields, Ari M. VanderWalde, John L. Marshall, Jimmy J. Hwang, Yasmine Baca, Michael J. Pishvaian, Axel Grothey, Joanne Xiu, and Michael Cerniglia
- Abstract
Supplemental Figure 1
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- 2023
40. Table S2 from Molecular Characterization of Appendiceal Goblet Cell Carcinoid
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Heinz-Josef Lenz, W. Michael Korn, John L. Marshall, Anthony F. Shields, Jimmy J. Hwang, Joanne Xiu, Andreas Seeber, Philip A. Philip, Richard M. Goldberg, Curtis Johnston, Joshua Millstein, Wu Zhang, Shivani Soni, Jingyuan Wang, Natsuko Kawanishi, Francesca Battaglin, Yasmine Baca, and Hiroyuki Arai
- Abstract
Copy number alteration frequency in appendiceal adenocarcinoma, NET and GCC
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- 2023
41. Figure S3 from Molecular Characterization of Appendiceal Goblet Cell Carcinoid
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Heinz-Josef Lenz, W. Michael Korn, John L. Marshall, Anthony F. Shields, Jimmy J. Hwang, Joanne Xiu, Andreas Seeber, Philip A. Philip, Richard M. Goldberg, Curtis Johnston, Joshua Millstein, Wu Zhang, Shivani Soni, Jingyuan Wang, Natsuko Kawanishi, Francesca Battaglin, Yasmine Baca, and Hiroyuki Arai
- Abstract
MCP-counter results for the three appendiceal tumor groups
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- 2023
42. Supplemental Table 1 from The Landscape of Glycogen Synthase Kinase-3 Beta Genomic Alterations in Cancer
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Benedito A. Carneiro, Wafik S. El-Deiry, Howard Safran, Lorin Crawford, Francis J. Giles, Andrew P. Mazar, W. Michael Korn, Sourat Darabi, Ari M. Vanderwalde, Benjamin A. Weinberg, Ira Winer, Fabio Tavora, Joanne Xiu, Yasmine Baca, and Brittany A. Borden
- Abstract
GSK-3B mutated tumors and PD-L1 expression - non-significant histologies
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- 2023
43. Supplemental File 1 from The Landscape of Glycogen Synthase Kinase-3 Beta Genomic Alterations in Cancer
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Benedito A. Carneiro, Wafik S. El-Deiry, Howard Safran, Lorin Crawford, Francis J. Giles, Andrew P. Mazar, W. Michael Korn, Sourat Darabi, Ari M. Vanderwalde, Benjamin A. Weinberg, Ira Winer, Fabio Tavora, Joanne Xiu, Yasmine Baca, and Brittany A. Borden
- Abstract
References analyzed as part of cBioPortal cohort
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- 2023
44. Data from Molecular Characterization of Appendiceal Goblet Cell Carcinoid
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Heinz-Josef Lenz, W. Michael Korn, John L. Marshall, Anthony F. Shields, Jimmy J. Hwang, Joanne Xiu, Andreas Seeber, Philip A. Philip, Richard M. Goldberg, Curtis Johnston, Joshua Millstein, Wu Zhang, Shivani Soni, Jingyuan Wang, Natsuko Kawanishi, Francesca Battaglin, Yasmine Baca, and Hiroyuki Arai
- Abstract
Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular profiles of GCC compared with other appendiceal tumors, such as adenocarcinomas and neuroendocrine tumors. A total of 495 appendiceal tumor samples (53 GCCs, 428 adenocarcinomas, and 14 neuroendocrine tumors) were tested with next-generation sequencing (NGS) on a 592-gene panel and IHC. Microsatellite instability (MSI)/mismatch repair (MMR) status was tested with a combination of NGS, IHC, and fragment analyses. Tumor mutational burden (TMB) was evaluated by NGS, and PD-L1 expression was tested by IHC (SP142). The most prevalent mutated genes within GCCs were TP53 (24.0%), ARID1A (15.4%), SMAD4 (9.4%), and KRAS (7.5%). Pathway-specific alterations were dominantly observed in cell cycle, MAPK, epigenetic, and TGFβ signaling pathways. GCCs as compared with adenocarcinomas exhibited significantly lower mutation rates in KRAS, GNAS, and APC, and significantly higher mutation rates in CDH1, CHEK2, CDC73, ERCC2, and FGFR2. GCCs as compared with neuroendocrine tumors showed significantly lower mutation rates in KRAS, APC, BRCA2, and FANCA. In GCCs, MSI high/MMR deficient, TMB high (≥17 mutations/Mb), and PD-L1 expression were seen in 0.0%, 0.0%, and 2.0% of tumors, respectively. No significant differences were observed in any immunotherapy-related markers examined when compared with adenocarcinomas and neuroendocrine tumors. In conclusion, GCCs had considerably distinct mutational profiles compared with appendiceal adenocarcinomas and neuroendocrine tumors. Understanding these molecular characteristics may be critical for the development of novel and more effective treatment strategies for GCC.
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- 2023
45. Supplemental Table 2 from The Landscape of Glycogen Synthase Kinase-3 Beta Genomic Alterations in Cancer
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Benedito A. Carneiro, Wafik S. El-Deiry, Howard Safran, Lorin Crawford, Francis J. Giles, Andrew P. Mazar, W. Michael Korn, Sourat Darabi, Ari M. Vanderwalde, Benjamin A. Weinberg, Ira Winer, Fabio Tavora, Joanne Xiu, Yasmine Baca, and Brittany A. Borden
- Abstract
Association between mismatch repair deficiency and differences in PD-L1 expression between GSK-3B-mutated and GSK-3B-wild type tumors
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- 2023
46. Data from Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers
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Heinz-Josef Lenz, Philip A. Philip, John L. Marshall, Anthony F. Shields, Jimmy J. Hwang, Benjamin A. Weinberg, W. Michael Korn, Joanne Xiu, Richard M. Goldberg, Derek Raghavan, Axel Grothey, Alberto Puccini, and Mohamed E. Salem
- Abstract
The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency (dMMR) status, and programmed cell death-ligand 1 (PD-L1) expression. Herein, we quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal cancers. Here, a total of 4,125 tumors from 14 different gastrointestinal cancer sites were studied using validated assays. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor specimens using the NextSeq platform. TML was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Microsatellite instability (MSI) was assessed using direct analysis of altered known MSI loci in the target regions of the sequenced genes. PD-L1 expression was analyzed by IHC. Interestingly, right-sided colon and small-bowel adenocarcinomas had the highest prevalence of TML-high tumors (14.6% and 10.2%, respectively). Pancreatic neuroendocrine tumors and gastrointestinal stromal tumors had the lowest rates of TML-high (1.3% and 0%, respectively). TML-high was strongly associated with MSI-H (P < 0.0001). However, all TML-high anal cancers (8.3%) were microsatellite stable (MSS). Higher PD-L1 expression was more likely to be seen in MSI compared with MSS tumors (20.6% vs. 7.8%, P < 0.0001).Implications: TML-high rate varied widely among gastrointestinal cancers. Although MSI is conceivably the main driver for TML-high, other factors may be involved. Future clinical trials are needed to evaluate whether the integration of TML, MSI, and PD-L1 could better identify potential responders to immunotherapy. Mol Cancer Res; 16(5); 805–12. ©2018 AACR.
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- 2023
47. Supplementary Table S2 from Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers
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Heinz-Josef Lenz, Philip A. Philip, John L. Marshall, Anthony F. Shields, Jimmy J. Hwang, Benjamin A. Weinberg, W. Michael Korn, Joanne Xiu, Richard M. Goldberg, Derek Raghavan, Axel Grothey, Alberto Puccini, and Mohamed E. Salem
- Abstract
Comparison between percentages of PD-L1 positive tumors using the cut-off at >5% (as in our analysis) and the cut-off >1% (as FDA-approved test for pembrolizumab use in advanced gastric and gastroesophageal junction adenocarcinomas).
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- 2023
48. Supplementary appendix from Molecular Characterization of Appendiceal Goblet Cell Carcinoid
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Heinz-Josef Lenz, W. Michael Korn, John L. Marshall, Anthony F. Shields, Jimmy J. Hwang, Joanne Xiu, Andreas Seeber, Philip A. Philip, Richard M. Goldberg, Curtis Johnston, Joshua Millstein, Wu Zhang, Shivani Soni, Jingyuan Wang, Natsuko Kawanishi, Francesca Battaglin, Yasmine Baca, and Hiroyuki Arai
- Abstract
The methods in assessing microsatellite instability (MSI) and mismatch repair (MMR) status
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- 2023
49. Supplementary Figure Legend from Association of Homologous Recombination–DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers
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Sunnie S. Kim, Jia Zeng, Richard M. Goldberg, Philip A. Philip, Mohamed Salem, W. Michael Korn, Heinz-Josef Lenz, Anthony F. Shields, Ari M. VanderWalde, John L. Marshall, Jimmy J. Hwang, Yasmine Baca, Michael J. Pishvaian, Axel Grothey, Joanne Xiu, and Michael Cerniglia
- Abstract
Supplementary Figure Legend
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- 2023
50. Supplementary Figure from Multi-omic Characterization of Pancreatic Ductal Adenocarcinoma Relates CXCR4 mRNA Expression Levels to Potential Clinical Targets
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Andreas Seeber, Dominik Wolf, Renate Pichler, Silvia Gasteiger, Chee-Keong Toh, Su-Pin Choo, Emil Lou, Heinz-Josef Lenz, Francesca Battaglin, Chadi Nabhan, W. Michael Korn, Michael Hall, John L. Marshall, Mohamed E. Salem, Anthony F. Shields, Angelica Petrillo, Richard M. Goldberg, Piotr Tymoszuk, Johannes Haybaeck, Joanne Xiu, Yasmine Baca, Andreas Pircher, Kai Zimmer, Agnieszka Martowicz, Gerold Untergasser, Alberto Puccini, and Florian Kocher
- Abstract
Supplementary Figure from Multi-omic Characterization of Pancreatic Ductal Adenocarcinoma Relates CXCR4 mRNA Expression Levels to Potential Clinical Targets
- Published
- 2023
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