A reduced panel of eight genes (ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53) as an estimator of the tumor mutational burden in chronic lymphocytic leukemia.
Adult
Aged
Ataxia Telangiectasia Mutated Proteins
/ genetics
Baculoviral IAP Repeat-Containing 3 Protein
/ genetics
Cost of Illness
Female
Humans
Karyopherins
/ genetics
Leukemia, Lymphocytic, Chronic, B-Cell
/ genetics
Male
Middle Aged
Mutation
Myeloid Differentiation Factor 88
/ genetics
Phosphoproteins
/ genetics
RNA Splicing Factors
/ genetics
Receptor, Notch1
/ genetics
Receptors, Cytoplasmic and Nuclear
/ genetics
Tumor Necrosis Factor alpha-Induced Protein 3
/ genetics
Tumor Suppressor Protein p53
/ genetics
Exportin 1 Protein
chronic lymphocytic leukemia
high-throughput sequencing
prognosis
tumor mutational burden
Journal
International journal of laboratory hematology
ISSN: 1751-553X
Titre abrégé: Int J Lab Hematol
Pays: England
ID NLM: 101300213
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
revised:
10
11
2020
received:
21
09
2020
accepted:
24
11
2020
pubmed:
17
12
2020
medline:
18
8
2021
entrez:
16
12
2020
Statut:
ppublish
Résumé
Mutational complexity or tumor mutational burden (TMB) influences the course of chronic lymphocytic leukemia (CLL). However, this information is not routinely used because TMB is usually obtained from whole genome or exome, or from large gene panel high-throughput sequencing. Here, we used the C-Harrel concordance index to determine the minimum panel of genes for which mutations predict treatment-free survival (TFS) as well as large resequencing panels. An eight gene estimator was defined encompassing ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53. TMB estimated from either a large panel of genes or the eight gene estimator was increased in treated patients or in those with a short TFS (<2 years), unmutated IGHV gene or with an unfavorable karyotype. Being an independent prognostic parameter, any mutation in the eight gene estimator predicted a shorter TFS better than Binet stage and IGHV mutational status among patients with an apparently non-progressive disease (TFS >6 months). Strikingly, the eight gene estimator was also highly informative for patients with Binet stage A CLL or with a good prognosis karyotype. These results suggest that the eight gene estimator, that is easily achievable by high-throughput resequencing, brings robust and valuable information that predicts evolution of untreated patients at diagnosis better than any other parameter.
Identifiants
pubmed: 33325634
doi: 10.1111/ijlh.13435
pmc: PMC8451785
doi:
Substances chimiques
Karyopherins
0
MYD88 protein, human
0
Myeloid Differentiation Factor 88
0
NOTCH1 protein, human
0
Phosphoproteins
0
RNA Splicing Factors
0
Receptor, Notch1
0
Receptors, Cytoplasmic and Nuclear
0
SF3B1 protein, human
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
BIRC3 protein, human
EC 2.3.2.27
Baculoviral IAP Repeat-Containing 3 Protein
EC 2.3.2.27
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
TNFAIP3 protein, human
EC 3.4.19.12
Tumor Necrosis Factor alpha-Induced Protein 3
EC 3.4.19.12
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
683-692Subventions
Organisme : Limoges University Hospital Center
Organisme : Ligue Contre le Cancer
Organisme : Rennes University Hospital Center
Informations de copyright
© 2020 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.
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