Prevalence of Clonal Hematopoiesis Mutations in Tumor-Only Clinical Genomic Profiling of Solid Tumors.
JAMA Oncol
; 4(11): 1589-1593, 2018 11 01.
Article
en En
| MEDLINE
| ID: mdl-29872864
ABSTRACT
Importance Although clonal hematopoiesis (CH) is well described in aging healthy populations, few studies have addressed the practical clinical implications of these alterations in solid-tumor sequencing. Objective:
To identify and quantify CH-related mutations in patients with solid tumors using matched tumor-blood sequencing, and to establish the proportion that would be misattributed to the tumor based on tumor-only sequencing (unmatched analysis). Design, Setting, andParticipants:
Retrospective analysis of samples from 17â¯469 patients with solid cancers who underwent prospective clinical sequencing of DNA isolated from tumor tissue and matched peripheral blood using the MSK-IMPACT assay between January 2014 and August 2017. Main Outcomes andMeasures:
We identified the presence of CH-related mutations in each patient's blood leukocytes and quantified the fraction of DNA molecules harboring the mutation in the corresponding matched tumor sample.Results:
The mean age of the 17â¯469 patients with cancer at sample collection was 59.2 years (range, 0.3-98.9 years); 53.6% were female. We identified 7608 CH-associated mutations in the blood of 4628 (26.5%) patients. A total of 1075 (14.1%) CH-associated mutations were also detectable in the matched tumor above established thresholds for calling somatic mutations. Overall, 912 (5.2%) patients would have had at least 1 CH-associated mutation erroneously called as tumor derived in the absence of matched blood sequencing. A total of 1061 (98.7%) of these mutations were absent from population scale databases of germline polymorphisms and therefore would have been challenging to filter informatically. Annotating variants with OncoKB classified 534 (49.7%) as oncogenic or likely oncogenic. Conclusions and Relevance This study demonstrates how CH-derived mutations could lead to erroneous reporting and treatment recommendations when tumor-only sequencing is used.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hematopoyesis
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Neoplasias
Tipo de estudio:
Guideline
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Observational_studies
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Prevalence_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
JAMA Oncol
Año:
2018
Tipo del documento:
Article