The contribution of large genomic rearrangements in BRCA1 and BRCA2 to South African familial breast cancer.

van der Merwe, Nerina C; Oosthuizen, Jaco; Theron, Magdalena; Chong, George; Foulkes, William D

van der Merwe, Nerina C; Oosthuizen, Jaco; Theron, Magdalena; Chong, George; Foulkes, William D.

Afiliación

van der Merwe NC; Division of Human Genetics, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa. vandermerwenc@ufs.ac.za.
Oosthuizen J; Division of Human Genetics, National Health Laboratory Services, Universitas Academic Hospital, Bloemfontein, South Africa. vandermerwenc@ufs.ac.za.
Theron M; Division of Human Genetics, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.
Chong G; Division of Human Genetics, National Health Laboratory Services, Universitas Academic Hospital, Bloemfontein, South Africa.
Foulkes WD; Division of Human Genetics, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa.

BMC Cancer ; 20(1): 391, 2020 May 06.

Article en En | MEDLINE | ID: mdl-32375709

RESUMEN

BACKGROUND: Pathogenic variants that occur in the familial breast cancer genes (BRCA1/2) lead to truncated ineffective proteins in the majority of cases. These variants are mostly represented by small deletions/insertions, nonsense- and splice-site variants, although some larger pathogenic rearrangements occur. Currently, their contribution to familial breast cancer (BC) and ovarian cancer (OVC) in South Africa (SA) is unknown. METHODS: Seven hundred and forty-four patients affected with BC or OVC were screened for larger genomic rearrangements (LGRs) by means of multiplex ligation-dependent probe amplification or Next Generation Sequencing using the Oncomine™ BRCA research assay. RESULTS: The patients represented mostly medium to high-risk families, but also included lower risk patients without a family history of the disease, diagnosed at an early age of onset (< 40 years). Eight LGRs were detected (1.1%); seven in BRCA1 with a single whole gene deletion (WGD) detected for BRCA2. These eight LGRs accounted for 8.7% of the 92 BRCA1/2 pathogenic variants identified in the 744 cases. The pathogenic LGRs ranged from WGDs to the duplication of a single exon. CONCLUSIONS: Larger rearrangements in BRCA1/2 contributed to the overall mutational burden of familial BC and OVC in SA. Almost a quarter of all pathogenic variants in BRCA1 were LGRs (7/30, 23%). The spectrum observed included two WGDs, one each for BRCA1 and BRCA2.

Asunto(s)

Proteína BRCA1/genética; Proteína BRCA2/genética; Biomarcadores de Tumor/genética; Neoplasias de la Mama/epidemiología; Neoplasias de la Mama/genética; Reordenamiento Génico; Mutación; Adulto; Femenino; Estudios de Seguimiento; Regulación Neoplásica de la Expresión Génica; Predisposición Genética a la Enfermedad; Pruebas Genéticas; Genómica; Humanos; Persona de Mediana Edad; Neoplasias Ováricas/epidemiología; Neoplasias Ováricas/genética; Pronóstico; Factores de Riesgo; Sudáfrica/epidemiología

Palabras clave

BRCA1/2; Familial breast cancer; Large genomic rearrangements; South Africa; Whole gene deletions

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Reordenamiento Génico / Biomarcadores de Tumor / Proteína BRCA1 / Proteína BRCA2 / Mutación Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Middle aged País/Región como asunto: Africa Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2020 Tipo del documento: Article País de afiliación: Sudáfrica Pais de publicación: Reino Unido

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