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Predicting the likelihood of a BRCA1/2 pathogenic variant being somatic by testing only tumour DNA in non-mucinous high-grade epithelial ovarian cancer.
Morgan, Robert D; Burghel, George J; Flaum, Nicola; Bulman, Michael; Smith, Philip; Clamp, Andrew R; Hasan, Jurjees; Mitchell, Claire; Salih, Zena; Woodward, Emma R; Lalloo, Fiona; Shaw, Joseph; Desai, Sudha; Crosbie, Emma J; Edmondson, Richard J; Schlecht, Helene; Wallace, Andrew J; Jayson, Gordon C; Evans, D Gareth R.
Afiliación
  • Morgan RD; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK robert.morgan7@nhs.net.
  • Burghel GJ; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK.
  • Flaum N; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
  • Bulman M; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK.
  • Smith P; Division of Evolution, Infection and Genomics, University of Manchester, Manchester, UK.
  • Clamp AR; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK.
  • Hasan J; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK.
  • Mitchell C; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
  • Salih Z; Division of Cancer Sciences, University of Manchester, Manchester, UK.
  • Woodward ER; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
  • Lalloo F; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
  • Shaw J; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
  • Desai S; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK.
  • Crosbie EJ; Department of Clinical Genetics, Manchester University NHS Foundation Trust, Manchester, UK.
  • Edmondson RJ; North West Genomic Laboratory Hub, Manchester University NHS Foundation Trust, Manchester, UK.
  • Schlecht H; Department of Clinical Genetics, Manchester University NHS Foundation Trust, Manchester, UK.
  • Wallace AJ; Department of Histopathology, Manchester University NHS Foundation Trust, Manchester, UK.
  • Jayson GC; Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK.
  • Evans DGR; Division of Cancer Sciences, University of Manchester, Manchester, UK.
J Clin Pathol ; 76(10): 684-689, 2023 Oct.
Article en En | MEDLINE | ID: mdl-35738887
AIMS: Clinical guidelines recommend testing both germline and tumour DNA for BRCA1/2 pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour BRCA1/2 PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline BRCA1/2 PVs. METHODS: An observational study that included all tumour BRCA1/2 PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022. All tumour BRCA1/2 PVs were compared with PVs recorded in a prospectively gathered pan-cancer germline BRCA1/2 (gBRCA) testing database for the same geographical region (gBRCA1 PVs=910 and gBRCA2 PVs=922). Tumour BRCA1/2 PVs were categorised as common (≥1%), uncommon (<1%) or absent from the germline database. RESULTS: One hundred and thirteen tumour BRCA1/2 PVs were detected in 111 NMEOC cases. There were 69 germline and 44 somatic variants. The mean age at diagnosis for gBRCA and somatic BRCA1/2 (sBRCA) PVs was 56.9 and 68.5 years, respectively (Student's t-test p<0.0001). All sBRCA PVs were detected in non-familial cases. All tumour BRCA1/2 PVs with a variant allele frequency (VAF) <35% in non-familial cases were somatic variants. Eighty-one per cent of germline-tumour BRCA1/2 PVs were present (common=31, uncommon=25) in the gBRCA testing database, while 89% of somatic-tumour BRCA1/2 PVs were absent (n=39). CONCLUSIONS: We predict the likelihood of a tumour BRCA1/2 PV being somatic is 99.8% in non-familial cases of NMEOC diagnosed aged ≥75, where the VAF is ≤30% and there is no regional germline commonality.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Proteína BRCA1 Tipo de estudio: Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: J Clin Pathol Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Proteína BRCA1 Tipo de estudio: Guideline / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: J Clin Pathol Año: 2023 Tipo del documento: Article Pais de publicación: Reino Unido