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Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations
- Source :
- Scientia
- Publication Year :
- 2023
- Publisher :
- Elsevier BV, 2023.
-
Abstract
- Germline; Tumour-only sequencing Línia germinal; Seqüenciació només de tumors Línea germinal; Secuenciación solo de tumors Background The European Society for Medical Oncology Precision Medicine Working Group (ESMO PMWG) was reconvened to update its 2018/19 recommendations on follow-up of putative germline variants detected on tumour-only sequencing, which were based on an analysis of 17 152 cancers. Methods We analysed an expanded dataset including 49 264 paired tumour-normal samples. We applied filters to tumour-detected variants based on variant allele frequency, predicted pathogenicity and population variant frequency. For 58 cancer-susceptibility genes, we then examined the proportion of filtered tumour-detected variants of true germline origin [germline conversion rate (GCR)]. We conducted subanalyses based on the age of cancer diagnosis, specific tumour types and ‘on-tumour’ status (established tumour-gene association). Results Analysis of 45 472 nonhypermutated solid malignancy tumour samples yielded 21 351 filtered tumour-detected variants of which 3515 were of true germline origin. 3.1% of true germline pathogenic variants were absent from the filtered tumour-detected variants. For genes such as BRCA1, BRCA2 and PALB2, the GCR in filtered tumour-detected variants was >80%; conversely for TP53, APC and STK11 this GCR was
- Subjects :
- Neoplasms [DISEASES]
neoplasias [ENFERMEDADES]
fenómenos genéticos::variación genética::mutación::mutación de la línea germinal [FENÓMENOS Y PROCESOS]
Anomalies cromosòmiques
terapéutica::medicina de precisión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]
Oncology
Medicina personalitzada
Hematology
Therapeutics::Precision Medicine [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Càncer - Aspectes genètics
Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation [PHENOMENA AND PROCESSES]
Subjects
Details
- ISSN :
- 09237534
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Annals of Oncology
- Accession number :
- edsair.doi.dedup.....ff765a5346fd311ae520e0d112a204fb