Studies

ID Title Abstract Investigator(s)
14 Longitudinal molecular and microenvironment evaluation of squamous cell pulmonary premalignancy Assessing archival lung squamous cell carcinoma cases that have premalignant lesions and prospectively collected pulmonary premalignant lesions, MCL investigators will identify molecular changes in premalignant pulmonary lesions in longitudinal setting using whole exome sequencing, gene expression profiling and multiplex immunofluorescence profiling of immune modulators in adenocarcinoma tumors and the associated premalignancies. Discovering critical neoepitopes and identifying longitudinal modulations in targetable neoepitopes and mediators of cellular immunity in pulmonary premalignancy will facilitate vaccine development for patients at the highest risk for progression to invasive lung cancer, transforming therapy and improving patient outcomes. Steve Dubinett
16 Integrated genomic/epigenomic and proteomic/glycoproteomic analysis of Indolent vs. Aggressive prostate cancer Using the independent but inter-related cohorts of aggressive vs. indolent prostate cancer developed at MCL sites Johns Hopkins and Stanford, the collaborative team will test if genetically and epigenetically encoded alterations in gene expression and protein expression/glycosylation can differentiate between indolent and aggressive cancer across both cohorts. The integrative approach will provide the most comprehensive information to date in understanding alterations in DNA -> RNA -> Proteins -> posttranslational modifications in aggressive vs. indolent prostate cancer Srinivasan Yegnasubramanian,Sharon Pitteri
19 DEFENSE study In this unique project, large palpable DCIS > 5cm without evidence of invasive cancer will be compared to age and molecularly matched invasive cancers from the I SPY 2 TRIAL of stage 2/3 tumors in an effort to understand what prevents invasion despite the development of a large palpable DCIS lesion. By exploring single cell sequencing, mutational analysis, immune multiplex profiling and stromal investigations, the team hopes to illuminate the mechanisms that prevent DCIS from progressing to invasive cancer. Laura Esserman,Robert West,Janet Stein
10 Vanderbilt University Medical Center Lung Adenocarcinoma CyTOF Mass cytometry data on lung adenocarcinoma human samples. Raw and preprocessed mass cytometry data on lung adenocarcinoma human samples collected during 2018-2019. Preprocessed data have undergone bead normalization and noise removal. Pierre Massion
22 Development of Common Immuno-Oncology Tools for Studying Microenvironmental Interactions Across Tumor Types The collaborative team will choose a standard set of Tumor Immune MicroEnvironment (TIME) markers that would be appropriate for use across tumor types and validate the marker panels and detection and quantitation methods across MCL sites. Using a high quality and commercially sourced reagents, and choosing a robust platform and methodology, a consensus approach for analysis of the will be developed by the MCL Pathology Working Group and CDMG, s. The approach will yield a well validated multiplex assay(s) that could ultimately be adopted for routine clinical use, in which the immune cell tumor infiltrates (ImmunoProfile) will be prognostic, though distributions and impacts may differ between tumor types, and will, in serial samples, aid in monitoring individual patient responses to immunotherapy. Alexander Borowsky
12 MCL Supplement: A Pre-Cancer Atlas (PCA) for Breast, Lung, Pancreas, and Prostate Pilot Project Characterization of molecular alterations in precancerous lesions and the corresponding microenvironment in four major organ sites in order to uncover the molecular and cellular determinants of premalignancy and establish standardized sequencing and immunohistochemistry protocols on FFPE precancerous tissue. Evaluation of the technical feasibility of single nuclei sequencing of small FFPE pre-cancer lesions. Successful completion of the proposed pilot study sets the stage for expansion and development of a comprehensive Pre-Cancer Atlas (PCA) as part of the NCI’s Cancer Moonshot Program. Avrum Spira
17 DCIS Consortium By building a rich comprehensive cohort of retrospective cases of ductal carcinoma in situ (DCIS) with matched DCIS or invasive recurrence and corresponding registry containing clinical, pathological, digital imaging, molecular markers and long-term >10 year follow-up data together with biospecimens, the collaborative team will improve understanding of the biology of DCIS. Within the consortium, the team will procure tissue blocks from recurrent cases with primary DCIS for a defined cohort to molecularly characterize both the index and recurrent lesions. Laura Esserman,Janet Stein
24 Collaborative Studies in an Animal Model for Pancreatic Cystic Neoplasia Using Dr. Maitra’s recently generated animal model of pancreatic cystic neoplasia, the collaborative team will perform basic cancer biology and translational cancer biomarker studies in a mouse model that can be extrapolated to human intraductal papillary mucinous neoplasms (IPMN) cohorts. The team will elucidate the global epigenomic, transcriptomic and protoemic alterations underlying the compound mutant Kras;Gnas model of pancreatic cystic neoplasia, identify circulating biomarkers of progression to invasive pancreatic ductal adenocarcinoma (PDAC) using the Kras;Gnas model of cystic neoplasia, and identify aberrantly expressed tumor-associate antigens as the potential basis of “precision immunotherapy.” Anirban Maitra
25 Molecular Profiling of Cystic Fluid for Improved Evaluation of Pancreatic Cysts Dr. Sen and team will perform ancillary molecular analyses of cyst fluid samples from MCL patient cohorts that are being evaluated for genetic drivers and physical microenvironment together with measurable humoral immune response in cystic lesions. Molecular analyses of cyst fluid will include next-generation sequencing based mutation analyses of a panel of driver genes and profiling of differentially abundant microRNAs and metabolites associated with predisposition and development of pancreatic ductal adenocarcinoma (PDAC). The approach will develop an integrated biomarker profile, developed from the ancillary molecular analyses of cyst fluid, with significantly improved sensitivity and specificity in discriminating pre-malignant from indolent cystic lesions than currently possible with the available diagnostic methods. Subrata Sen
26 University of Vermont Molecular Characterization Laboratory (Breast) Dr. Stein and team will leverage existing national and Vermont statewide registries of integrated clinical, radiology, pathology, treatment and outcomes data with matching biospecimens from breast cancer patients to identify molecular and cellular signatures in tumor microenvironment that are predictive of aggressiveness of early stage screen-detected breast cancers. Their approach is to characterize the cell composition and cell-specific gene expression patterns with focus on tumor microenvironments of aggressive interval- and symptom-detected breast cancers. Janet Stein,Donald Weaver,Brian Sprague
27 MD Anderson Cancer Center Molecular and Cellular Characterization Laboratory (Pancreatic) Dr. Maitra and team seek to develop a framework that integrates quantitative assessment of diagnostic imaging data with the host immune responses and systemic (circulating) biomarkers elicited by an underlying pancreatic cystic neoplasm, in order to generate algorithms that can reliably distinguish between indolent and aggressive lesions. Understanding the interactions between biology and physics of cystic lesions of the pancreas, where the genetic drivers of pancreatic cyst formation interact with the physical microenvironment to fuel malignant progression reflected in measurable imaging features and humoral immune responses, will offer transformative scientific and clinical approaches to pancreatic cancer and its early detection. Anirban Maitra
28 UCSF Molecular and Cellular Characterization Laboratory (Breast) Dr. Esserman and team seek to develop better biologic discriminators of IDLE (indolent lesions of epithelial origin), ultralow, low and interval breast cancers (usually highly proliferative hormone receptor (HR)- positive and negative and/or HER2 positive tumors). Their overall approach, which is made possible by their network of international collaborators and unique data sets, is to retrospectively optimize and prospectively validate new and emergent molecular, morphometric and tumor immune microenvironment assays and to prospectively add the context of germline predisposition. Laura Esserman
29 UCLA-BU Stanford Molecular and Cellular Characterization Laboratory (Lung) Dr. Dubinett and team seek to understand the pathways underlying heterogeneity in screen-detected lung cancers through both integrated systems analysis of molecular, microenvironment and imaging characteristics of screen-detected lesions, and comparison of molecular and cellular characteristics between screen-detected and non-screen-detected tumors. Steve Dubinett
30 Johns Hopkins Molecular and Cellular Characterization Laboratory (Prostate) Using a large institutional database of patients who have undergone radical prostatectomies, Dr. DeMarzo and multi-disciplinary team will develop integrated genomic, epigenetic and expression profiling signatures of indolent and aggressive prostate tumors in both white and African American men. Molecular biomarkers will then be validated using immunohistochemistry and/or in situ hybridization, and further validated in relation to patient outcomes, to yield novel biomarkers that can be used in clinical practice to guide appropriate treatment and reduce overtreatment. Angelo De Marzo
31 Stanford Molecular and Cellular Characterization Laboratory (Prostate) Dr. Brooks and team will focus on prostate evolution and heterogeneity. They will investigate the early genomic evolution of good and adverse outcome prostate cancer through examination of genomic and gene-expression changes early in the development and in the evolution of prostate cancer. From this they will also evaluate candidate prognostic genomic features. Additionally, the team will define the genomic heterogeneity of good and adverse outcome prostate cancer through examination of genomic and gene expression changes, and protein expression and glycoproteomic alterations in localized prostate cancer. Leveraging this work they will investigate correlations of integrated genomic, transcript, protein and glycoprotein changes in localized prostate cancers with clinical outcomes. James Brooks
32 Vanderbilt Molecular and Cellular Characterization Laboratory (Lung) Dr. Massion and team will integrate quantitative structural image analysis, single cell and molecular analysis of early stage adenocarcinoma of the lung from screen- or incidentally-detected lung nodules to improve discrimination of indolent from aggressive cancers and develop optimal approaches of intervention. Their approach includes collection, integration and analysis of clinical, structural imaging, cellular and molecular attributes of screen-detected non-solid, part-solid, and solid malignant modules as well as non-screen detected lung adenocarcinomas to discover biological determinants of indolent tumor behavior. They aim to impact clinical interventions for both indolent and aggressive tumors and develop strategies to avoid morbidities associated with overdiagnosis in lung cancer screening efforts. Pierre Massion
33 Team 37 CTIIP Animal Models Use-cases for the CTIIP for animal and human modeling Alexander Borowsky
5 Differential gene expression in lung adenocarcinoma Lung adenocarcinoma is caused by the combination of genetic and environmental effects, and smoking plays an important role in the disease development. Exploring the gene expression profile and identifying genes that are shared or vary between smokers and nonsmokers with lung adenocarcinoma will provide insights into the etiology of this complex cancer. We obtained RNA-seq data from paired normal and tumor tissues from 34 nonsmoking and 34 smoking patients with lung adenocarcinoma (GEO: GSE40419). R Bioconductor, edgeR, was adopted to conduct differential gene expression analysis between paired normal and tumor tissues. A generalized linear model was applied to identify genes that were differentially expressed in nonsmoker and smoker patients as well as genes that varied between these two groups. We identified 2273 genes that showed differential expression with FDR < 0.05 and |logFC| >1 in nonsmoker tumor versus normal tissues; 3030 genes in the smoking group; and 1967 genes were common to both groups. Sixty-eight and 70% of the identified genes were downregulated in nonsmoking and smoking groups, respectively. The 20 genes such as SPP1, SPINK1, and FAM83A with largest fold changes in smokers also showed similar large and highly significant fold changes in nonsmokers and vice versa, showing commonalities in expression changes for adenocarcinomas in both smokers and nonsmokers for these genes. We also identified 175 genes that were significantly differently expressed between tumor samples from nonsmoker and smoker patients. Gene expression profile varied substantially between smoker and nonsmoker patients with lung adenocarcinoma. Smoking patients overall showed far more complicated disease mechanism and have more dysregulation in their gene expression profiles. Our study reveals pathogenetic differences in smoking and nonsmoking patients with lung adenocarcinoma from transcriptome analysis. We provided a list of candidate genes for further study for disease detection and treatment in both smoking and nonsmoking patients with lung adenocarcinoma. Yafang Li
35 1.0 Athena-IHC4 with Swedish Breast Cancer Study Slides from 1976-1985 breast cancer study in Sweden stained for IHC4 for WSI and QIA. Alexander Borowsky
36 RNA sequencing of FFPE Samples of screen-detected or incidental Lung Tumors RNAseq of FFPE Samples of Lung Tumors (screen-detected vs. incidental) Avrum Spira
PCA Pilot Project

MCL Supplement: A Pre-Cancer Atlas (PCA) for Breast, Lung, Pancreas, and Prostate Pilot Project