Breast cancer research and treatment · 2007
Identification of a novel BRCA1 large genomic rearrangement in a Spanish breast/ovarian cancer family.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Palanca Suela Sarai, Esteban Cardeñosa Eva, Barragán González Eva, Oltra Soler Silvestre, de Juan Jiménez Inma, Chirivella González Isabel, Segura Huerta Angel, Guillén Ponce Carmen, Martínez de Dueñas Eduardo, Bolufer Gilabert Pascual, Group for Assessment of Hereditary Cancer of Valencia Community
Аннотация
BACKGROUND: Alterations in BRCA1 gene are responsible for the majority of hereditary breast and/or ovarian cancers. However, the frequency of detected germline mutations is lower than expected by linkage analysis. Standard PCR-based screening methods are mainly used for detecting mutations, but the large genomic rearrangements are commonly overlooked. The purpose of this study was to confirm and characterize a novel deletion identified in BRCA1 gene which has not yet been reported to date.
METHODS: Multiplex ligation-dependent probe amplification was used to analyze BRCA1 rearrangements in 255 unrelated index patients with familial breast and/or ovarian cancer negative for BRCA1/BRCA2 mutations studied in Program of Genetic Counselling on Cancer of Valencia Community (Spain). The breakpoints of detected novel rearrangement were characterized by sequencing.
RESULTS AND DISCUSSION: Five different rearrangements in the BRCA1 gene were identified in five unrelated index patients out of the 225 (2%). We found four large genomic rearrangements already described consisting in a 1A/1B and 2 deletion; deletion of exons 5-7; deletion of exons 8-13; exon 20 deletion. Additionally, we found the novel g.8097_22733del14637 deletion that encompasses exons 3-5. This deletion affects the RING domain of the BRCA1 protein and it is suggestive of having a negative impact on its function.
CONCLUSION: The new mutation here reported broadens the mutational spectrum of large rearrangements. Furthermore, the five large rearrangements found in patients non-carriers of BRCA1/BRCA2 mutations reinforce the need of studying BRCA1 large genomic rearrangements in genetic counselling programs.
METHODS: Multiplex ligation-dependent probe amplification was used to analyze BRCA1 rearrangements in 255 unrelated index patients with familial breast and/or ovarian cancer negative for BRCA1/BRCA2 mutations studied in Program of Genetic Counselling on Cancer of Valencia Community (Spain). The breakpoints of detected novel rearrangement were characterized by sequencing.
RESULTS AND DISCUSSION: Five different rearrangements in the BRCA1 gene were identified in five unrelated index patients out of the 225 (2%). We found four large genomic rearrangements already described consisting in a 1A/1B and 2 deletion; deletion of exons 5-7; deletion of exons 8-13; exon 20 deletion. Additionally, we found the novel g.8097_22733del14637 deletion that encompasses exons 3-5. This deletion affects the RING domain of the BRCA1 protein and it is suggestive of having a negative impact on its function.
CONCLUSION: The new mutation here reported broadens the mutational spectrum of large rearrangements. Furthermore, the five large rearrangements found in patients non-carriers of BRCA1/BRCA2 mutations reinforce the need of studying BRCA1 large genomic rearrangements in genetic counselling programs.