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

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

Authors:	Ptashkin, R. N.; Ewalt, M. D.; Jayakumaran, G.; Kiecka, I.; Bowman, A. S.; Yao, J. J.; Casanova, J.; Lin, Y. T. D.; Petrova-Drus, K.; Mohanty, A. S.; Bacares, R.; Benhamida, J.; Rana, S.; Razumova, A.; Vanderbilt, C.; Balakrishnan Rema, A.; Rijo, I.; Son-Garcia, J.; de Bruijn, I.; Zhu, M.; Lachhander, S.; Wang, W.; Haque, M. S.; Seshan, V. E.; Wang, J.; Liu, Y.; Nafa, K.; Borsu, L.; Zhang, Y.; Aypar, U.; Suehnholz, S. P.; Chakravarty, D.; Park, J. H.; Abdel-Wahab, O.; Mato, A. R.; Xiao, W.; Roshal, M.; Yabe, M.; Batlevi, C. L.; Giralt, S.; Salles, G.; Rampal, R.; Tallman, M.; Stein, E. M.; Younes, A.; Levine, R. L.; Perales, M. A.; van den Brink, M. R. M.; Dogan, A.; Ladanyi, M.; Berger, M. F.; Brannon, A. R.; Benayed, R.; Zehir, A.; Arcila, M. E.
Article Title:	Enhanced clinical assessment of hematologic malignancies through routine paired tumor and normal sequencing
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. © 2023, The Author(s).
Keywords:	controlled study; gene mutation; major clinical study; single nucleotide polymorphism; somatic mutation; genetics; mutation; janus kinase 2; allogeneic stem cell transplantation; flow cytometry; neoplasm; neoplasms; clinical assessment; cohort analysis; gene frequency; brca2 protein; protein p53; hematologic malignancy; hematologic neoplasms; fluorescence in situ hybridization; somatic hypermutation; dna; blood sampling; atm protein; genomics; rhoa guanine nucleotide binding protein; immunomodulation; tumor; myeloproliferative neoplasm; hematologic disease; ephrin receptor a5; dna methyltransferase 3a; cell; copy number variation; single nucleotide polymorphism array; diffuse large b cell lymphoma; blood system disorder; high throughput sequencing; allelic imbalance; high-throughput nucleotide sequencing; isocitrate dehydrogenase 2; dna sequencing; cancer; humans; human; article; tumor mutational burden
Journal Title:	Nature Communications
Volume:	14
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2023-10-28
Start Page:	6895
Language:	English
DOI:	10.1038/s41467-023-42585-9
PUBMED:	37898613
PROVIDER:	scopus
PMCID:	PMC10613284
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85175159436&doi=10.1038%2fs41467-023-42585-9&partnerID=40&md5=dbe03932f591d0bd6cd06d5ce2099b91
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in [the PubMed record/PDF/the PubMed record and PDF]. Corresponding MSK authors are Mark D. Ewalt, Ahmet Zehir and Maria E. Arcila -- Source: Scopus