TY - JOUR
T1 - Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes
AU - The MMRF CoMMpass Network
AU - Skerget, Sheri
AU - Penaherrera, Daniel
AU - Chari, Ajai
AU - Jagannath, Sundar
AU - Siegel, David S.
AU - Vij, Ravi
AU - Orloff, Gregory
AU - Jakubowiak, Andrzej
AU - Niesvizky, Ruben
AU - Liles, Darla
AU - Berdeja, Jesus
AU - Levy, Moshe
AU - Wolf, Jeffrey
AU - Usmani, Saad Z.
AU - Steis, Ronald
AU - Srinivas, Shanti
AU - Roy, Vivek
AU - Rodríguez, Paula
AU - Oriol, Albert
AU - Kumar, Shaji
AU - Krsnik, Isabel
AU - Matkiwsky, May
AU - Girnius, Saulias
AU - Conde, Miguel
AU - Chandra, Sumeet
AU - Anderson, Robert
AU - Solomon, William
AU - Richards, Donald
AU - Patel, Dilip
AU - Menter, Alex
AU - Kaya, Hakan
AU - Hsu, Gerald
AU - Hassoun, Hani
AU - Bargay, Joan
AU - Anderson, Larry
AU - Abella, Eugenia
AU - Yalamachili, Madhuri
AU - Wachsman, William
AU - Volterra, Fabio
AU - Onitilo, Adedayo
AU - Min, Fredrick
AU - Shieh, Marie
AU - Bar, Michael
AU - Ngaiza, Justinian
AU - Harris, Wayne
AU - Sebag, Michael
AU - Robles, Robert
AU - Yost, Kathleen
AU - Grossbard, Michael
AU - Lewis, De Quincy
AU - Kambhampati, Suman
AU - Costello, Caitlin
AU - Chinea, Anabelle
AU - Silva, Carlos
AU - Balaraman, Rama
AU - Martinez-Chamorro, Carmen
AU - Granell, Miquel
AU - Azaceta, Gemma
AU - Fonseca, Rafael
AU - Kuzma, Charles
AU - Klein, Leonard
AU - de Larrea, Carlos Fernández
AU - Dodlapati, Jyothi
AU - Shao, Spencer
AU - Graham, Mark
AU - Harroff, Allyson
AU - Milner, Carter
AU - Chu, Michael
AU - Lunning, Matthew
AU - Silbermann, Rebecca
AU - Mannem, Siva
AU - Sampol, Antonia
AU - Rios, Pablo
AU - Paganini, Juan Vazquez
AU - Bahlis, Nizar
AU - Dakhil, Shaker
AU - Trudel, Suzanne
AU - Hernández, Miguel
AU - Gasparetto, Cristina
AU - Ascensao, Joao
AU - Zonder, Jeffrey
AU - Benson, Don
AU - Meehan, Kenneth
AU - Rifkin, Robert
AU - Christofferson, Austin W.
AU - Nasser, Sara
AU - Aldrich, Jessica L.
AU - Legendre, Christophe
AU - Benard, Brooks
AU - Miller, Chase
AU - Turner, Bryce
AU - Kurdoglu, Ahmet
AU - Washington, Megan
AU - Yellapantula, Venkata
AU - Adkins, Jonathan R.
AU - Cuyugan, Lori
AU - Boateng, Martin
AU - Helland, Adrienne
AU - Kyman, Shari
AU - McDonald, Jackie
AU - Reiman, Rebecca
AU - Stephenson, Kristi
AU - Tassone, Erica
AU - Blanski, Alex
AU - Livermore, Brianne
AU - Kirchhoff, Meghan
AU - Rohrer, Daniel C.
AU - D’Agostino, Mattia
AU - Gamella, Manuela
AU - Collison, Kimberly
AU - Stumph, Jennifer
AU - Kidd, Pam
AU - Donnelly, Andrea
AU - Zaugg, Barbara
AU - Toone, Maureen
AU - McBride, Kyle
AU - DeRome, Mary
AU - Rogers, Jennifer
AU - Craig, David
AU - Liang, Winnie S.
AU - Gutierrez, Norma C.
AU - Jewell, Scott D.
AU - Carpten, John
AU - Anderson, Kenneth C.
AU - Cho, Hearn Jay
AU - Auclair, Daniel
AU - Lonial, Sagar
AU - Keats, Jonathan J.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/9
Y1 - 2024/9
N2 - Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation’s Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study (NCT01454297) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.
AB - Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation’s Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study (NCT01454297) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.
UR - http://www.scopus.com/inward/record.url?scp=85201525988&partnerID=8YFLogxK
U2 - 10.1038/s41588-024-01853-0
DO - 10.1038/s41588-024-01853-0
M3 - Article
C2 - 39160255
AN - SCOPUS:85201525988
SN - 1061-4036
VL - 56
SP - 1878
EP - 1889
JO - Nature Genetics
JF - Nature Genetics
IS - 9
ER -