Microsatellite instability detection using a large next-generation sequencing cancer panel across diverse tumour types.
J Clin Pathol
; 73(2): 83-89, 2020 Feb.
Article
en En
| MEDLINE
| ID: mdl-31530574
ABSTRACT
AIM:
Microsatellite instability (MSI), a hallmark of DNA mismatch repair deficiency, is a key molecular biomarker with multiple clinical implications including the selection of patients for immunotherapy, identifying patients who may have Lynch syndrome and predicting prognosis in patients with colorectal tumours. Next-generation sequencing (NGS) provides the opportunity to interrogate large numbers of microsatellite loci concurrently with genomic variants. We sought to develop a method to detect MSI that would not require paired normal tissue and would leverage the sequence data obtained from a broad range of tumours tested using our 467-gene NGS Columbia Combined Cancer Panel (CCCP).METHODS:
Altered mononucleotide and dinucleotide microsatellite loci across the CCCP region of interest were evaluated in clinical samples encompassing a diverse range of tumour types. The number of altered loci was used to develop a decision tree classifier model trained on the retrospectively collected cohort of 107 clinical cases sequenced by the CCCP assay.RESULTS:
The classifier was able to correctly classify all cases and was then used to analyse a test set of clinical cases (n=112) and was able to correctly predict their MSI status with 100% sensitivity and specificity. Analysis of recurrently altered loci identified alterations in genes involved in DNA repair, signalling and transcriptional regulation pathways, many of which have been implicated in MSI tumours.CONCLUSION:
This study highlights the utility of this approach, which should be applicable to laboratories performing similar testing.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
/
Perfilación de la Expresión Génica
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Inestabilidad de Microsatélites
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Detección Precoz del Cáncer
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Secuenciación de Nucleótidos de Alto Rendimiento
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Neoplasias
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article