2010
DOI: 10.1200/jco.2009.27.2997
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Abstract: A B S T R A C T PurposeThe prevalence of BRCA1/2 mutations in germline DNA from unselected ovarian cancer patients is 11% to 15.3%. It is important to determine the frequency of somatic BRCA1/2 changes, given the sensitivity of BRCA-mutated cancers to poly (ADP ribose) polymerase-1 (PARP1) inhibitors and platinum analogs. Patients and MethodsIn 235 unselected ovarian cancers, BRCA1/2 was sequenced in 235, assessed by copy number analysis in 95, and tiling arrays in 65. 113 tumors were sequenced for TP53. BRCA1… Show more

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Cited by 334 publications
(294 citation statements)
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References 17 publications
(4 reference statements)
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“…Genomic aberrations affecting BRCA1 and BRCA2 are most common in high‐grade serous OCs, although they also occur in other subtypes [Hennessy et al., 2010; Alsop et al., 2012]. Our results support that the majority of the carriers of germline mutations in BRCA1 and BRCA2 develop (high‐grade) serous OCs [Boyd et al., 2000; Hennessy et al., 2010]; however, a significant subset (17%) of OCs derived from patients with germline mutations in BRCA1 and BRCA2 reveal a different histological phenotype. Therefore, we recommend that sequencing of BRCA1 and BRCA2 should be considered in all patients with OCs irrespective of their histological subtype.…”
Section: Discussionmentioning
confidence: 99%
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“…Genomic aberrations affecting BRCA1 and BRCA2 are most common in high‐grade serous OCs, although they also occur in other subtypes [Hennessy et al., 2010; Alsop et al., 2012]. Our results support that the majority of the carriers of germline mutations in BRCA1 and BRCA2 develop (high‐grade) serous OCs [Boyd et al., 2000; Hennessy et al., 2010]; however, a significant subset (17%) of OCs derived from patients with germline mutations in BRCA1 and BRCA2 reveal a different histological phenotype. Therefore, we recommend that sequencing of BRCA1 and BRCA2 should be considered in all patients with OCs irrespective of their histological subtype.…”
Section: Discussionmentioning
confidence: 99%
“…Approximately 10%–15% of all OC patients carry a pathogenic germline aberration in BRCA1 or BRCA2 [Daly et al., 2010; Hennessy et al., 2010; Kanchi et al., 2014]. Loss of heterozygosity (LOH) of the wild‐type allele is the tumor‐initiating second hit in the majority of these patients [Foster et al., 1996; Berchuck et al., 1998].…”
Section: Introductionmentioning
confidence: 99%
“…[18][19][20][21][22][23][24] Germline mutations in BRCA1 and BRCA2 are present in B18% of ovarian cancer patients with high-grade serous carcinoma. [25][26][27] When combined with BRCA deficiencies that result from somatic mutations or epigenetic silencing, it appears that up to half of all high-grade serous ovarian cancers (hereditary and sporadic) have BRCA dysfunction. 15,[26][27][28][29][30] BRCA1 and BRCA2 genes encode functionally related proteins that play a critical role in repair of DNA double-strand breaks.…”
mentioning
confidence: 99%
“…[25][26][27] When combined with BRCA deficiencies that result from somatic mutations or epigenetic silencing, it appears that up to half of all high-grade serous ovarian cancers (hereditary and sporadic) have BRCA dysfunction. 15,[26][27][28][29][30] BRCA1 and BRCA2 genes encode functionally related proteins that play a critical role in repair of DNA double-strand breaks. [31][32][33] Loss of BRCA function results in development of chromosomal instability.…”
mentioning
confidence: 99%
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