Feasibility and clinical utility of comprehensive genomic profiling of hematological malignancies.
comprehensive genomic profiling
hematological malignancy
next-generation sequencing
precision medicine
somatic alteration
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
revised:
26
04
2022
received:
12
02
2022
accepted:
12
05
2022
pubmed:
18
5
2022
medline:
10
8
2022
entrez:
17
5
2022
Statut:
ppublish
Résumé
Identification of genetic alterations through next-generation sequencing (NGS) can guide treatment decision-making by providing information on diagnosis, therapy selection, and prognostic stratification in patients with hematological malignancies. Although the utility of NGS-based genomic profiling assays was investigated in hematological malignancies, no assays sufficiently cover driver mutations, including recently discovered ones, as well as fusions and/or pathogenic germline variants. To address these issues, here we have devised an integrated DNA/RNA profiling assay to detect various types of somatic alterations and germline variants at once. Particularly, our assay can successfully identify copy number alterations and structural variations, including immunoglobulin heavy chain translocations, IKZF1 intragenic deletions, and rare fusions. Using this assay, we conducted a prospective study to investigate the feasibility and clinical usefulness of comprehensive genomic profiling for 452 recurrently altered genes in hematological malignancies. In total, 176 patients (with 188 specimens) were analyzed, in which at least one alteration was detected in 171 (97%) patients, with a median number of total alterations of 7 (0-55). Among them, 145 (82%), 86 (49%), and 102 (58%) patients harbored at least one clinically relevant alteration for diagnosis, treatment, and prognosis, respectively. The proportion of patients with clinically relevant alterations was the highest in acute myeloid leukemia, whereas this assay was less informative in T/natural killer-cell lymphoma. These results suggest the clinical utility of NGS-based genomic profiling, particularly for their diagnosis and prognostic prediction, thereby highlighting the promise of precision medicine in hematological malignancies.
Identifiants
pubmed: 35579198
doi: 10.1111/cas.15427
pmc: PMC9357666
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2763-2777Subventions
Organisme : National Cancer Center Research and Development Funds
ID : 30-A-1
Organisme : Otsuka Pharmaceutical Co., Ltd.
Informations de copyright
© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Mayo Clin Proc. 2013 Apr;88(4):360-76
pubmed: 23541011
Lancet Oncol. 2015 Sep;16(9):1111-1122
pubmed: 26256760
Blood. 2018 Aug 9;132(6):587-597
pubmed: 29884741
Blood. 2016 Sep 1;128(9):1226-33
pubmed: 27458004
Cancer Sci. 2022 Aug;113(8):2763-2777
pubmed: 35579198
N Engl J Med. 2018 Apr 12;378(15):1396-1407
pubmed: 29641966
Nature. 2020 Feb;578(7793):82-93
pubmed: 32025007
Drug Discov Today. 2015 Dec;20(12):1470-5
pubmed: 26494142
Nat Med. 2016 Dec;22(12):1488-1495
pubmed: 27841873
Genet Med. 2021 Nov;23(11):2029-2037
pubmed: 34211152
Blood. 2016 Jul 7;128(1):e1-9
pubmed: 27121471
Nucleic Acids Res. 2013 Apr;41(7):e89
pubmed: 23471004
Nat Genet. 2015 Nov;47(11):1304-15
pubmed: 26437031
Leukemia. 2009 Dec;23(12):2210-21
pubmed: 19798094
Cancer Cell. 2020 Apr 13;37(4):551-568.e14
pubmed: 32289277
Nat Genet. 2016 May;48(5):569-74
pubmed: 27019113
Blood. 2018 Jun 21;131(25):2745-2760
pubmed: 29540348
Nat Rev Cancer. 2021 Feb;21(2):122-137
pubmed: 33328584
Cell. 2013 Sep 26;155(1):27-38
pubmed: 24074859
Blood. 2018 Aug 16;132(7):758-761
pubmed: 29930010
Nat Genet. 2017 Aug;49(8):1274-1281
pubmed: 28671687
Blood Cancer Discov. 2020 Jul;1(1):96-111
pubmed: 32793890
Cancer Sci. 2020 Sep;111(9):3367-3378
pubmed: 32619037
Nature. 2015 Oct 22;526(7574):525-30
pubmed: 26466571
N Engl J Med. 2016 Jun 9;374(23):2209-2221
pubmed: 27276561
Blood. 2022 Feb 17;139(7):967-982
pubmed: 34695199
Blood. 2016 Jun 16;127(24):3004-14
pubmed: 26966091
N Engl J Med. 2018 Oct 11;379(15):1416-1430
pubmed: 30304655
Nat Genet. 2019 Feb;51(2):296-307
pubmed: 30643249
Nat Rev Cancer. 2016 May 25;16(6):387-98
pubmed: 27220482
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
Blood. 2017 Jan 26;129(4):424-447
pubmed: 27895058
Nat Genet. 2013 Oct;45(10):1113-20
pubmed: 24071849
Cancer Sci. 2019 Apr;110(4):1464-1479
pubmed: 30737998
N Engl J Med. 2009 Jan 29;360(5):470-80
pubmed: 19129520
Leukemia. 2019 Dec;33(12):2867-2883
pubmed: 31092896
N Engl J Med. 2014 Jun 12;370(24):2286-94
pubmed: 24869598
Nature. 2012 Jan 11;481(7382):506-10
pubmed: 22237025
N Engl J Med. 2014 Sep 11;371(11):1005-15
pubmed: 25207766