Mayo Clinic Laboratory and Pathology Research Roundup: October 26

By Samantha Rossi • October 26, 2020

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The research roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.

Featured Abstract

Inherited causes of clonal haematopoiesis in 97,691 whole genomes.

Age is the dominant risk factor for most chronic human diseases, but the mechanisms through which ageing confers this risk are largely unknown¹. The age-related acquisition of somatic mutations that lead to clonal expansion in regenerating haematopoietic stem cell populations has recently been associated with both haematological cancer^2-4 and coronary heart disease⁵-this phenomenon is termed clonal haematopoiesis of indeterminate potential (CHIP)⁶. Simultaneous analyses of germline and somatic whole-genome sequences provide the opportunity to identify root causes of CHIP. Here we analyse high-coverage whole-genome sequences from 97,691 participants of diverse ancestries in the National Heart, Lung, and Blood Institute Trans-omics for Precision Medicine (TOPMed) programme, and identify 4,229 individuals with CHIP. We identify associations with blood cell, lipid and inflammatory traits that are specific to different CHIP driver genes. Association of a genome-wide set of germline genetic variants enabled the identification of three genetic loci associated with CHIP status, including one locus at TET2 that was specific to individuals of African ancestry. In silico-informed in vitro evaluation of the TET2 germline locus enabled the identification of a causal variant that disrupts a TET2 distal enhancer, resulting in increased self-renewal of haematopoietic stem cells. Overall, we observe that germline genetic variation shapes haematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal haematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues. Via Nature.

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Published to PubMed This Week

• Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.
  Cancer Discovery
• Th17-Inducing Autologous Dendritic Cell Vaccination Promotes Antigen-Specific Cellular and Humoral Immunity in Ovarian Cancer Patients.
  Nature Communications
• Laboratory Analysis of Acylcarnitines, 2020 Update: A Technical Standard of the American College of Medical Genetics and Genomics (ACMG).
  Genetic Medicine
• Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
  American Journal of Human Genetics
• i-IFTA and Chronic Active T-Cell Mediated Rejection: A Tale of 2 (DeKAF) Cohorts.
  American Journal of Transplants
• Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial.
  Journal of Urology
• Fatty Acid Synthase Is a Key Enabler for Endocrine Resistance in Heregulin-Overexpressing Luminal B-Like Breast Cancer.
  International Journal of Molecular Science
• Association of Amyloid Angiopathy with Microbleeds in Logopenic Progressive Aphasia: An Imaging-Pathology Study.
  European Journal of Neurology
• Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.
  Journal of Cardiac Failures
• Ceramides Improve Atherosclerotic Cardiovascular Disease Risk Assessment beyond Standard Risk Factors.
  Clinical Chimica Acta

Samantha Rossi

Samantha Rossi is a Digital Marketing Manager at Mayo Clinic Laboratories. She supports marketing strategies for product management and specialty testing. Samantha has worked at Mayo Clinic since 2019.