@article{3d39d573b9a54c36937473939c7232ad,
title = "Genetic subtypes of smoldering multiple myeloma are associated with distinct pathogenic phenotypes and clinical outcomes",
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.",
author = "Mark Bustoros and Shankara Anand and Romanos Sklavenitis-Pistofidis and Robert Redd and Boyle, {Eileen M.} and Benny Zhitomirsky and Dunford, {Andrew J.} and Tai, {Yu Tzu} and Chavda, {Selina J.} and Cody Boehner and Neuse, {Carl Jannes} and Mahshid Rahmat and Ankit Dutta and Tineke Casneuf and Raluca Verona and Efstathis Kastritis and Lorenzo Trippa and Chip Stewart and Walker, {Brian A.} and Davies, {Faith E.} and Dimopoulos, {Meletios Athanasios} and Bergsagel, {P. Leif} and Kwee Yong and Morgan, {Gareth J.} and Fran{\c c}ois Aguet and Gad Getz and Ghobrial, {Irene M.}",
note = "Funding Information: We would like to acknowledge Anna Justis, Ph.D. for scientific writing support and Jean-Baptiste Alberge for critical review of the manuscript. We thank all the patients and their families for their contributions to this study. This study was supported in part by grants from the National Institutes of Health (NIH; R01CA205954), Multiple Myeloma Research Foundation (MMRF) Prevention Project-Perelman Family Foundation Early Disease Translational Research Program, Leukemia and Lymphoma Society (LLS) Specialized Center of Research (SCOR) program, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and Cancer Research UK (CRUK) Early Detection and Diagnosis Program (Grant Number: A28770). K.Y. receives funding from the National Institute for Health Research-University College London Hospitals (NIHR UCLH) Biomedical Research Centre. Selina Chavda receives funding from the Medical Research Council (MRC), UK. This research was also supported by a Stand Up To Cancer (SU2C) Dream Team grant (SU2C‐AACR‐DT‐28‐18). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of Stand Up To Cancer. Opinions, interpretations, conclusions, and recommendations are those of the author(s) and are not necessarily endorsed by Stand Up To Cancer, the Entertainment Industry Foundation, or the American Association for Cancer Research. Funding Information: We would like to acknowledge Anna Justis, Ph.D. for scientific writing support and Jean-Baptiste Alberge for critical review of the manuscript. We thank all the patients and their families for their contributions to this study. This study was supported in part by grants from the National Institutes of Health (NIH; R01CA205954), Multiple Myeloma Research Foundation (MMRF) Prevention Project-Perelman Family Foundation Early Disease Translational Research Program, Leukemia and Lymphoma Society (LLS) Specialized Center of Research (SCOR) program, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and Cancer Research UK (CRUK) Early Detection and Diagnosis Program (Grant Number: A28770). K.Y. receives funding from the National Institute for Health Research-University College London Hospitals (NIHR UCLH) Biomedical Research Centre. Selina Chavda receives funding from the Medical Research Council (MRC), UK. This research was also supported by a Stand Up To Cancer (SU2C) Dream Team grant (SU2C‐AACR‐DT‐28‐18). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of Stand Up To Cancer. Opinions, interpretations, conclusions, and recommendations are those of the author(s) and are not necessarily endorsed by Stand Up To Cancer, the Entertainment Industry Foundation, or the American Association for Cancer Research. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-30694-w",
language = "English (US)",
volume = "13",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}