Molecular phenotyping of small cell lung cancer using targeted cfDNA profiling of transcriptional regulatory regions.
Sci Adv
; 10(15): eadk2082, 2024 Apr 12.
Article
en En
| MEDLINE
| ID: mdl-38598634
ABSTRACT
We report an approach for cancer phenotyping based on targeted sequencing of cell-free DNA (cfDNA) for small cell lung cancer (SCLC). In SCLC, differential activation of transcription factors (TFs), such as ASCL1, NEUROD1, POU2F3, and REST defines molecular subtypes. We designed a targeted capture panel that identifies chromatin organization signatures at 1535 TF binding sites and 13,240 gene transcription start sites and detects exonic mutations in 842 genes. Sequencing of cfDNA from SCLC patient-derived xenograft models captured TF activity and gene expression and revealed individual highly informative loci. Prediction models of ASCL1 and NEUROD1 activity using informative loci achieved areas under the receiver operating characteristic curve (AUCs) from 0.84 to 0.88 in patients with SCLC. As non-SCLC (NSCLC) often transforms to SCLC following targeted therapy, we applied our framework to distinguish NSCLC from SCLC and achieved an AUC of 0.99. Our approach shows promising utility for SCLC subtyping and transformation monitoring, with potential applicability to diverse tumor types.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
/
Carcinoma Pulmonar de Células Pequeñas
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Ácidos Nucleicos Libres de Células
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Neoplasias Pulmonares
Límite:
Humans
Idioma:
En
Revista:
Sci Adv
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos