Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes
Year: 2022
Type: article
Study design: Observational Study
Abstract: Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with significant heterogeneity in disease progression. Existing clinical models of progression risk do not fully capture this heterogeneity. Here we integrate 42 genetic alterations from 214 SMM patients using unsupervised binary matrix factorization (BMF) clustering and identify six distinct genetic subtypes. These subtypes are differentially associated with established MM-related RNA signatures, oncogenic and immune transcriptional profiles, and evolving clinical biomarkers. Three genetic subtypes are associated with increased risk of progression to active MM in both the primary and validation cohorts, indicating they can be used to better predict high and low-risk patients within the currently used clinical risk stratification models.
Source: Nature Communications
Authors: Mark Bustoros, Shankara Anand, Romanos Sklavenitis-Pistofidis, Robert Redd, Eileen M. Boyle, Benny Zhitomirsky, Andrew J. Dunford, Yu-Tzu Tai, Selina J. Chavda, Cody Boehner, Carl Jannes Neuse, Mahshid Rahmat, Ankit Dutta, Tineke Casneuf, Raluca Verona, Efstathis Kastritis, Lorenzo Trippa, Chip Stewart, Brian A. Walker, Faith E. Davies, Meletios-Athanasios Dimopoulos, P. Leif Bergsagel, Kwee Yong, Gareth J. Morgan, François Aguet, Gad Getz, Irene M. Ghobrial
Institutions: Dana-Farber Cancer Institute, Weill Cornell Medicine, Broad Institute, Boston University, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, University College London, University of Münster, Janssen (Belgium), National and Kapodistrian University of Athens, Indiana University Indianapolis, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Mayo Clinic, Mayo Clinic in Arizona, Massachusetts General Hospital, Dana-Farber/Harvard Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: American Association for Cancer Research, Multiple Myeloma Research Foundation, Leukemia and Lymphoma Society, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Entertainment Industry Foundation, Cancer Research UK, National Institute for Health and Care Research, University College London, University College London Hospitals NHS Foundation Trust, National Institutes of Health, Stand Up To Cancer, Medical Research Council, National Cancer Institute, National Institute of General Medical Sciences
OpenAlex ID: W4282944983