Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia

Telomere length is an independent prognostic marker in MDS but not in de novo AML

Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements which drives progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 Myelodysplasia (MDS) and 95 de novo Acute Myeloid Leukaemia (AML) patients. Despite the MDS cohort being older they had significantly longer telomeres than the AML cohort (P<.0001) where telomere length was also significantly shorter in younger AML patients (age <60) (P = .02) and in FLT3 ITD mutated AML patients (P = .03). Using a previously determined telomere length threshold for telomere dysfunction (3.81kb) did not provide prognostic resolution in AML (HR = 0.68, P = .2). In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5.0, P <.0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and IPSS score (HR = 2.27, P < .0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS

Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients

Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer

Finding the missing and unknown: Novel educational approaches to warming up cold cases

In recent years, students in police academies and higher education institutions around the world have worked together to analyse cold cases including long-term missing persons cases in collaboration with investigators and prosecutors. In 2020, three European organisations, the Police Expert Network on Missing Persons (PEN-MP), AMBER Alert Europe and Locate International, succeeded in connecting these educational organisations enabling them to work collectively on cases and conduct cold case analyses (CCA) across international borders. The International Cold Case Analysis Project (ICCAP) learning objectives were to 1) collect the necessary information about the victim, 2) reconstruct the crime, and 3) investigate trace control. In a learning objective-based evaluation using Computer-Assisted Web Interviewing, 76 participating students from the German and International ICCAP teams were asked to complete a pre- and post-review questionnaire to self-assess their personal competence development. Participants reported significant increases in competence in all evaluated areas, thus demonstrating that authentic and relevant collaborations can enrich the learning environment, promote the use of professional skills, and provide significant knowledge exchange opportunities between academia and industry. Drawing on case studies of cold case missing persons' investigations and unidentified found remains, this article shares how university academics, students and community volunteers can work together nationally and internationally to find out what has happened to missing people and how we can more effectively identify the previously unidentified. In so doing, we share the expertise required to progress these cold cases and provide recommendations to support other institutions and organisations in adopting this innovative approach

Arizona State Museum Archaeological Series No. 207

Power and Economy in Early Classic Period Hohokam Society: An Archaeological Perspective from the Marana Mound Site edited by James M. Bayman, Paul R. Fish, and Suzanne K. Fish with contributions by Frank E. Bayham, James M. Bayman, Margaret E. Beck, Michael J. Boley, Sergio F. Castro-Reino, Christopher Descantes, Paul R. Fish, Suzanne K. Fish, Michael D. Glascock, Deanna Grimstead, Karla Hansen-Speer, Cory Harris, Karen G. Harry, Abigail L. Holeman, R. Emerson Howell, Jeffrey A. Homburg, Phillip O. Leckman, Elizabeth Miksa, Christopher Roos, Robert J. Speakman. Arizona State Museum Archaeological Series 207.Foreword: This volume introduces the research design for investigations undertaken at the Marana Mound site (AZ AA:12:251 [ASM]) following the conclusion of the Northern Tucson Basin Survey (NTBS) in 1990, a brief summary of major fi ndings at this Early Classic center, and selected studies on more focused topics. Results of the previous NTBS survey have been published in a variety of venues, including journal articles, book chapters, monographs, and graduate student theses and dissertations. Comprehensive summary publications are The Marana Community in the Hohokam World edited by Suzanne K. Fish, Paul R. Fish, and John H. Madsen (1992a), The Northern Tucson Basin Survey: Research Directions and Background Studies edited by John H. Madsen, Paul R. Fish, and Suzanne K. Fish (1993), and Between Desert and River: Hohokam Settlement and Land Use in the Los Robles Community by Christian E. Downum (1993). The selected studies in this volume are an outgrowth of archaeological field classes and field schools that were held at the Marana Mound site during spring semesters between 1990 and 2003. The contributions were initially presented at a symposium at the 69th Annual Meeting of the Society for American Archaeology (SAA) in Montreal, Canada, in 2004, and have been modified over the intervening years. As of this writing, studies of Marana collections continue and some of the findings reported here undoubtedly will be refined by this ongoing research as well as future analyses. In the meantime, these studies offer valuable insights on the organization of Hohokam society during the Early Classic Period (ca. AD 1150-1300) from the perspective of one uniquely well-preserved locale—the Marana Mound site.Contents / List of Figures / List of Tables / Foreword / Acknowledgements / Chapter 1: Introduction: The Marana Mound Site by Suzanne K. Fish, Paul R. Fish, and James M. Bayman / Chapter 2: From Households to Middens: Refuse Deposition Patterns in Two Settlements / Chapter 3: Analysis of Adobe Architecture at the Marana Platform Mound Site / Chapter 4: Compound Redefinition at the Marana Mound Site by Cory Harris / Chapter 5: Analysis of Plant Remains from the Marana Mound Site by Karla Hansen-Speer / Chapter 6: Feasting at the Marana Platform Mound by Deanna Grimstead and Frank E. Bayham / Chapter 7: Polishing Stones and Their Story: A Look at Production at the Marana Platform Mound Site by Abigail L. Holeman / Chapter 8: Production and Exchange of Plain Ware Ceramics in the Marana Community by Karen G. Harry, Robert J. Speakman, Elizabeth Miksa, Sergio F. Castro-Reino, Christopher Descantes, Paul R. Fish, Suzanne K. Fish, and Michael D. Glascock / Chapter 9: Obsidian Acquisition and (Re)Distribution at the Marana Platform Mound Site by Michael J. Boley / Chapter 10: Visibility, Perception, and Power at the Marana Platform Mound: A Spatial Analysis by Phillip O. Leckman / Reference CitedThis title from the ASM Archaeological Series is made available by the Arizona State Museum and University of Arizona Libraries. If you have questions about this title, please contact Jannelle Weakly at the Arizona State Museum, (520) 621-6311, [email protected]