Year: 2020
Type: article
Study design: Observational Study
Abstract: Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient′s life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant.
Source: Nature Communications
Authors: Heather J. Landau, Venkata Yellapantula, Benjamin T. Diamond, Even H. Rustad, Kylee H. Maclachlan, Gunes Gundem, Juan Medina-Martinez, Juan Arango Ossa, Max F. Levine, Yangyu Zhou, Rajya Kappagantula, Priscilla Baez, Marc Attiyeh, Alvin Makohon-Moore, Lance Zhang, Eileen M. Boyle, Cody Ashby, Patrick Blaney, Minal Patel, Yanming Zhang, Ahmet Dogan, David J. Chung, Sergio Giralt, Oscar B. Lahoud, Jonathan U. Peled, Michael Scordo, Gunjan Shah, Hani Hassoun, Neha S. Korde, Alexander M. Lesokhin, Sydney Lu, Sham Mailankody, Urvi Shah, Eric Smith, Malin L. Hultcrantz, Gary A. Ulaner, Frits van Rhee, Gareth J. Morgan, Ola Landgren, Elli Papaemmanuil, Christine Iacobuzio-Donahue, Francesco Maura
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: American Society of Hematology, International Myeloma Foundation, Memorial Sloan-Kettering Cancer Center, Royal College of Pathologists of Australasia, Society of Memorial Sloan Kettering, Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, Parker Institute for Cancer Immunotherapy, Haematology Society of Australia and New Zealand, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute
Awards: G1496737397, Interrogating the Evolutionary Dynamics of Cancer for Clinical Benefit and Actionability, Transition to Metastatic State: Lung Cancer, Pancreatic Cancer and Brain Metastasis, G2227505777, G2246262118, G289723095, G3316582232, G4102770861, Microbiota mechanisms and biomarkers in GVHD, G9000003249, Cancer Center Support Grant
OpenAlex ID: W3042890009