Enhanced clinical assessment of hematologic malignancies through routine paired tumor and normal sequencing

Ryan N. Ptashkin, Mark D. Ewalt (), Gowtham Jayakumaran, Iwona Kiecka, Anita S. Bowman, JinJuan Yao, Jacklyn Casanova, Yun-Te David Lin, Kseniya Petrova-Drus, Abhinita S. Mohanty, Ruben Bacares, Jamal Benhamida, Satshil Rana, Anna Razumova, Chad Vanderbilt, Anoop Balakrishnan Rema, Ivelise Rijo, Julie Son-Garcia, Ino Bruijn, Menglei Zhu, Sean Lachhander, Wei Wang, Mohammad S. Haque, Venkatraman E. Seshan, Jiajing Wang, Ying Liu, Khedoudja Nafa, Laetitia Borsu, Yanming Zhang, Umut Aypar, Sarah P. Suehnholz, Debyani Chakravarty, Jae H. Park, Omar Abdel-Wahab, Anthony R. Mato, Wenbin Xiao, Mikhail Roshal, Mariko Yabe, Connie Lee Batlevi, Sergio Giralt, Gilles Salles, Raajit Rampal, Martin Tallman, Eytan M. Stein, Anas Younes, Ross L. Levine, Miguel-Angel Perales, Marcel R. M. Brink, Ahmet Dogan, Marc Ladanyi, Michael F. Berger, A. Rose Brannon, Ryma Benayed, Ahmet Zehir () and Maria E. Arcila ()
Additional contact information
Ryan N. Ptashkin: Memorial Sloan Kettering Cancer Center
Mark D. Ewalt: Memorial Sloan Kettering Cancer Center
Gowtham Jayakumaran: Memorial Sloan Kettering Cancer Center
Iwona Kiecka: Memorial Sloan Kettering Cancer Center
Anita S. Bowman: Memorial Sloan Kettering Cancer Center
JinJuan Yao: Memorial Sloan Kettering Cancer Center
Jacklyn Casanova: Memorial Sloan Kettering Cancer Center
Yun-Te David Lin: Memorial Sloan Kettering Cancer Center
Kseniya Petrova-Drus: Memorial Sloan Kettering Cancer Center
Abhinita S. Mohanty: Memorial Sloan Kettering Cancer Center
Ruben Bacares: Memorial Sloan Kettering Cancer Center
Jamal Benhamida: Memorial Sloan Kettering Cancer Center
Satshil Rana: Memorial Sloan Kettering Cancer Center
Anna Razumova: Memorial Sloan Kettering Cancer Center
Chad Vanderbilt: Memorial Sloan Kettering Cancer Center
Anoop Balakrishnan Rema: Memorial Sloan Kettering Cancer Center
Ivelise Rijo: Memorial Sloan Kettering Cancer Center
Julie Son-Garcia: Memorial Sloan Kettering Cancer Center
Ino Bruijn: Memorial Sloan Kettering Cancer Center
Menglei Zhu: Memorial Sloan Kettering Cancer Center
Sean Lachhander: Memorial Sloan Kettering Cancer Center
Wei Wang: Memorial Sloan Kettering Cancer Center
Mohammad S. Haque: Memorial Sloan Kettering Cancer Center
Venkatraman E. Seshan: Memorial Sloan Kettering Cancer Center
Jiajing Wang: Memorial Sloan Kettering Cancer Center
Ying Liu: Memorial Sloan Kettering Cancer Center
Khedoudja Nafa: Memorial Sloan Kettering Cancer Center
Laetitia Borsu: Memorial Sloan Kettering Cancer Center
Yanming Zhang: Memorial Sloan Kettering Cancer Center
Umut Aypar: Memorial Sloan Kettering Cancer Center
Sarah P. Suehnholz: Memorial Sloan Kettering Cancer Center
Debyani Chakravarty: Memorial Sloan Kettering Cancer Center
Jae H. Park: Memorial Sloan Kettering Cancer Center
Omar Abdel-Wahab: Memorial Sloan Kettering Cancer Center
Anthony R. Mato: Memorial Sloan Kettering Cancer Center
Wenbin Xiao: Memorial Sloan Kettering Cancer Center
Mikhail Roshal: Memorial Sloan Kettering Cancer Center
Mariko Yabe: Memorial Sloan Kettering Cancer Center
Connie Lee Batlevi: Memorial Sloan Kettering Cancer Center
Sergio Giralt: Memorial Sloan Kettering Cancer Center
Gilles Salles: Memorial Sloan Kettering Cancer Center
Raajit Rampal: Memorial Sloan Kettering Cancer Center
Martin Tallman: Memorial Sloan Kettering Cancer Center
Eytan M. Stein: Memorial Sloan Kettering Cancer Center
Anas Younes: Memorial Sloan Kettering Cancer Center
Ross L. Levine: Memorial Sloan Kettering Cancer Center
Miguel-Angel Perales: Memorial Sloan Kettering Cancer Center
Marcel R. M. Brink: Memorial Sloan Kettering Cancer Center
Ahmet Dogan: Memorial Sloan Kettering Cancer Center
Marc Ladanyi: Memorial Sloan Kettering Cancer Center
Michael F. Berger: Memorial Sloan Kettering Cancer Center
A. Rose Brannon: Memorial Sloan Kettering Cancer Center
Ryma Benayed: Memorial Sloan Kettering Cancer Center
Ahmet Zehir: Memorial Sloan Kettering Cancer Center
Maria E. Arcila: Memorial Sloan Kettering Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Genomic profiling of hematologic malignancies has augmented our understanding of variants that contribute to disease pathogenesis and supported development of prognostic models that inform disease management in the clinic. Tumor only sequencing assays are limited in their ability to identify definitive somatic variants, which can lead to ambiguity in clinical reporting and patient management. Here, we describe the MSK-IMPACT Heme cohort, a comprehensive data set of somatic alterations from paired tumor and normal DNA using a hybridization capture-based next generation sequencing platform. We highlight patterns of mutations, copy number alterations, and mutation signatures in a broad set of myeloid and lymphoid neoplasms. We also demonstrate the power of appropriate matching to make definitive somatic calls, including in patients who have undergone allogeneic stem cell transplant. We expect that this resource will further spur research into the pathobiology and clinical utility of clinical sequencing for patients with hematologic neoplasms.

Date: 2023
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DOI: 10.1038/s41467-023-42585-9

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