Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

Research on Counternarratives of Curriculum in Schools, Neighborhoods, and Communities in the US South

This is a continuation of dialogue on pushing boundaries in dissertation work as we continue to research on and write about the counternarratives of curriculum of schools, neighborhoods, and communities in the U. S. South. We explore creative ways to push methodological and representational boundaries to liberate dissertation writing by diving into life and writing into contradiction in schools, families, and communities in the U. S. South. Through visual/graphic/multimedia presentations, reader’s theater, spoken word, drama, and performance, the presenters will illustrate diverse forms of dissertation research and representations such as critical race narrative inquiry, critical geography/critical dis/ability studies, critical multiracial/mixed racial fictional auto/biographical inquiry, multiperspectival poetic inquiry, multiperspectival cultural studies, womanist currere, critical portraiture, memoir, fiction, oral history, documentary film, and painting. Innovative writings engendered from the inquiries will be demonstrated. Potentials, challenges, and future directions of creative inquiries and representations will be discussed. There are three purposes to this session. One purpose of this presentation is to share our experience of moving beyond methodological and representational boundaries to liberate dissertation writing by diving into life and writing into contradiction in schools, families, and communities in the U. S. South. The second purpose is to explore creative ways to engage in and write about research and embed inquiry in school, neighborhood, and community life to transform research into positive social and educational change. Another purpose is to engage the audience from diverse research paradigms in discussions on how diverse forms of curriculum inquiry and modes of representation and expression help capture cultural, linguistic, and socio-political poetics of personal, community, and historical narrative; address pressing issues and contemporary concerns; make impact on practice, policy, and historical, social, political, economic, geographical, cultural, linguistic, and ecological contexts; and advance curriculum theorizing and praxis toward social justice. The potentials, challenges, and future directions of various inquiries and representations are also discussed. We begin with an overview of diverse forms of curriculum inquiry and modes of representation and expression with the intent to imagine and recognize possibilities to push methodological and representational boundaries to liberate dissertation writing. We then invigorate exploratory conversations on forms of inquiry modes of representation and expression that challenge traditional ways of engaging in, interpreting, and writing about research. We invite curriculum inquirers to engage in activist oriented research and writing, transcend inquiry boundaries, raise challenging questions, transgress orthodoxy and dogma, and research silenced narratives of underrepresented or disenfranchised individuals and groups with hearts and minds (Ayers, 2004, 2006; He & Ayers, 2008; hooks, 1994, 2003) to build a long term and heart felt participatory movement to promote cultural, linguistic, and ecological diversity and flourishing plurality of humanity (Schubert, 2009). The power of such inquiries and representations lies in its potential to locate experience within complex social, cultural, and linguistic contexts and enable researchers to dive into life and write into contradiction. Such inquiries and representations enable the researchers to develop a deeper understanding of cultural research phenomena, inquiry contexts, modes of inquiry, forms of representation, and possible educational and social changes engendered by research and writing. Such inquiries and representations thrive on the passionate involvement, commitment and advocacy of the researchers, and help cultivate hope and possibilities for better lives as experienced in diverse schools, families, and communities. Please list individual presentations within the session (see attached for details) Individual Presentations Within the Session: Presentation #1: Research on Counternarratives of Curriculum in Schools, Neighborhoods, and Communities in the South Ming Fang He, Georgia Southern University Presentation #2: Research on the Lived Experience of Chinese International Students at a Non-Research I University in the U. S. South Yiming Jin, Georgia Southern University (TA & Doctoral Fellow in Curriculum Studies; Email: Yiming Jin, or ) Presentation #3: Counternarratives of Students with Significant Disabilities in One Rural Elementary School in Georgia Christy Howard, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Email: Christy Howard ) Presentation #4: Counterstories of African American Students in a Racialized School System in Georgia Chanda R. Hardiman, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Chanda R. Hardiman or ) Presentation #5: Culturally Contested Curriculum? Developing Culturally Sustaining Curriculum for the Classical Education of African American Students in an Urban Georgia Middle School Ellen M. Hotchkiss, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Ellen M. Hotchkiss ) Presentation #6: Como se dice Learning: A Critical Ethnographic Linguistic Inquiry into Successful Foreign Language Learners in A Suburban Southeastern US High School Kathleen E. Barbara, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Kathleen E. Barbara ) Presentation #7: Teaching with Passion: Indigenous Thought and Storywork Ashley E. West, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Ashley E. West ) Presentation #8: Culturally Contested Curriculum? Developing Culturally Sustaining Curriculum for the Classical Education of African American Students in an Urban Georgia Middle School Mary E. Negley, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Mary Negley or ) Presentation #9: Cross-Cultural Narrative Inquiry into the Experience of Chinese Ethnic Minority Teachers Studying in US Universities Ru Li, Georgia Southern University (TA, Instructor, & Doctoral Candidate in Curriculum Studies; Emails: Ru Li ) Presentation #10: Using Fiction in High School English Language Classrooms Eden A. Evans, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Eden A. Evans or ) Presentation #11: Languages, Cultures, and Identities: Experiences of HBCU Students in a Study Abroad Program in Costa Rica Irina Tedrick, Georgia Southern University (University Instructor & Doctoral Candidate in Curriculum Studies; Emails: Irina Tedrick or ) Presentation #12: Place, Space, and the Education of Auditory-Oral Deaf Students in the Inclusion Classrooms: A Teacher’s Performative Memoir Tracy L. Edenfield, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Tracy L. Edenfield or ) Presentation #13: Teaching with Passion and Compassion: Stories of Successes, Obstacles, and Dreams of Dedicated Educators in Public Schools in Georgia Erin P. Scroggs, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Erin P. Scroggs or ) Presentation #14: Between Suicide and Murder : Post-Structural Reflections on Language Learning, Power, and Alterity Jennifer J. Bowers, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Jennifer J. Bowers or ) Presentation #15: Exploring Unwanted Roads Traveled on the Curriculum Roadmap of Life Katherine F. Wyatt, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Katherine F. Wyatt or ) Presentation #16: Joys and Fears of A Black Mother Raising Her Son in the US South: A Memoir Alethea Coleman, Georgia Southern University (Teacher & Doctoral Candidate in Curriculum Studies; Emails: Alethea Coleman