Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Sep 8;8(60):101325-101332.
doi: 10.18632/oncotarget.20722. eCollection 2017 Nov 24.

Detection of BRCA1/2 mutations in circulating tumor DNA from patients with ovarian cancer

Magdalena Ratajska  1 , Magdalena Koczkowska  1 , Monika Żuk  1   2 , Adam Gorczyński  3 , Alina Kuźniacka  1   2 , Maciej Stukan  4 , Wojciech Biernat  3 , Janusz Limon  1   2 , Bartosz Wasąg  1   2
Affiliations

Detection of BRCA1/2 mutations in circulating tumor DNA from patients with ovarian cancer

Magdalena Ratajska et al. Oncotarget. .

Abstract

Approximately 25% of patients with ovarian cancer harbor a pathogenic BRCA1/2 mutation that has been associated with favorable responses for targeted therapy with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors compared to wild-type individuals. The overall frequency of germline and somatic BRCA1/2 alterations is estimated at 13-15% and 3-10%, respectively. A high incidence of BRCA1/2 somatic variants significantly increases the number of patients eligible for treatment with PARP1 inhibitors. Here, we assessed circulating tumor DNA (ctDNA) from 121 patients with ovarian cancer for BRCA1/2 mutational analysis by next generation sequencing. A total number of patients carrying the pathogenic BRCA1/2 variants was 30/121 (24.8%), including 22 and 7 individuals with exclusively germline or somatic mutations, respectively and one patient with variants of both origin. Among this cohort, more than one known pathogenic BRCA1 and/or BRCA2 alterations were identified in 7/30 individuals. The most recurrent mutations were detected in the BRCA1 gene: c.5266dupC (p.Gln1756Profs*74) with the frequency of ~18%, followed by c.3756_3759del (p.Ser1253Argfs*10) and c.181T>G (p.Cys61Gly). In seven (5.8%) patients, coincidence of two or more BRCA1/2 pathogenic mutations have been identified. Our results clearly demonstrate that the detection of both germline and somatic BRCA1/2 mutations in ctDNA from ovarian cancer patients is feasible and may be a valuable complementary tool for identification of somatic alterations when the standard diagnostic procedures are insufficient. Finally, ctDNA can potentially allow to monitor the efficacy of PARP1 inhibitors and to detect a secondary reversion BRCA1/2 mutations.

Keywords: BRCA1/2; PARP1 inhibitor; ctDNA; next-generation sequencing; ovarian cancer.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. The spectrum of pathogenic germline and somatic mutations in the BRCA1 and BRCA2 genes detected in 121 ctDNA samples from ovarian cancer patients
Each number in the circle corresponds with the total number of samples with specific alteration. The germline or somatic origin of mutation is depicted with the red and green color code, respectively. The figure was prepared using the ProteinPaint application [31].
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–1403. doi: 10.1016/j.ejca.2012.12.027. - DOI - PubMed
    1. Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, LaPolla J, Hoffman M, Martino MA, Wakeley K, Wilbanks G, Nicosia S, Cantor A, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104:2807–2816. doi: 10.1002/cncr.21536. - DOI - PubMed
    1. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Fan I, Tang J, Li S, Zhang S, Shaw PA, Narod SA. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst. 2006;98:1694–1706. doi: 10.1093/jnci/djj465. - DOI - PubMed
    1. Merajver SD, Pham TM, Caduff RF, Chen M, Poy EL, Cooney KA, Weber BL, Collins FS, Johnston C, Frank TS. Somatic mutations in the BRCA1 gene in sporadic ovarian tumours. Nat Genet. 1995;9:439–443. doi: 10.1038/ng0495-439. - DOI - PubMed
    1. Foster KA, Harrington P, Kerr J, Russell P, DiCioccio RA, Scott IV, Jacobs I, Chenevix-Trench G, Ponder BA, Gayther SA. Somatic and germline mutations of the BRCA2 gene in sporadic ovarian cancer. Cancer Res. 1996;56:3622–3625. - PubMed

LinkOut - more resources