Detection of Biallelic Loss of DNA Repair Genes in Formalin-Fixed, Paraffin-Embedded Tumor Samples Using a Novel Tumor-Only Sequencing Panel.
J Mol Diagn
; 25(5): 295-310, 2023 05.
Article
en En
| MEDLINE
| ID: mdl-36944408
ABSTRACT
Patient selection for synthetic lethal-based cancer therapy may be improved by assessment of gene-specific loss of heterozygosity (LOH) and biallelic loss of function (LOF). This report describes SyNthetic lethal Interactions for Precision Diagnostics (SNiPDx), a targeted next-generation sequencing (NGS) panel for detection of LOH and biallelic LOF alterations in 26 target genes focused on DNA damage response pathways, in tumor-only formalin-fixed, paraffin-embedded (FFPE) samples. NGS was performed across all exons of these 26 genes and encompassed a total of 7632 genome-wide single-nucleotide polymorphisms on genomic DNA from 80 FFPE solid tumor samples. The Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing algorithm was optimized to assess tumor purity and copy number based on heterozygous single-nucleotide polymorphisms. SNiPDx demonstrated high sensitivity (95%) and specificity (91%) for LOH detection compared with whole genome sequencing. Positive agreement with local NGS-based testing in the detection of genetic alterations was 95%. SNiPDx detected 93% of biallelic ATM LOF mutations, 100% of ATM single-nucleotide variants and small insertions/deletions, and 100% of all ATM LOH status events identified by orthogonal NGS-based testing. SNiPDx is a novel, clinically feasible test for analysis of allelic status in FFPE tumor samples, which demonstrated high accuracy when compared with other NGS-based approaches in clinical use.
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1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article