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
. 2013 Dec;231(4):449-56.
doi: 10.1002/path.4252.

KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma

Yvonne T Tsang  1 , Michael T Deavers, Charlotte C Sun, Suet-Yan Kwan, Eric Kuo, Anais Malpica, Samuel C Mok, David M Gershenson, Kwong-Kwok Wong
Affiliations

KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma

Yvonne T Tsang et al. J Pathol. 2013 Dec.

Abstract

BRAF and KRAS mutations in ovarian serous borderline tumours (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or whether those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumour samples from 23 recurrent LGSC patients with a known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for five patients, and either OSBTs or LGSCs were available for another 18 patients. Tumour cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumours that appeared to have wild-type KRAS by conventional PCR-Sanger sequencing were further analysed by full COLD (co-amplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR-Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in ten patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in seven OSBT samples and six LGSC samples. Surprisingly, patients with the KRAS G12V mutation have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumour cells with or without detectable KRAS mutations.

Keywords: BRAF; COLD-PCR; KRAS; deep sequencing; mutation; ovarian low-grade serous carcinoma; serous borderline tumour.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement: The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Sanger sequencing traces for OSBT samples from two patients and recurrent LGSC samples from the same patients. A. Standard PCR, LGSC. B. Standard PCR, OSBT. C. Full COLD-PCR, OSBT.
Figure 2
Figure 2
Hematoxylin-eosin-stained slides of OSBT samples and recurrent LGSC samples from two patients.
Figure 3
Figure 3
Kaplan-Meier curves for three groups of patients with recurrent LGSC and different KRAS mutations: KRAS G12V (n = 5), KRAS G12D (n = 8), and wild-type KRAS or rare KRAS mutations (n = 10). Cum, cumulative; wt, wild type.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wong KK, Gershenson D. The continuum of serous tumors of low malignant potential and low-grade serous carcinomas of the ovary. Dis Markers. 2007;23:377–387. - PMC - PubMed
    1. Vang R, Shih Ie M, Kurman RJ. Ovarian low-grade and high-grade serous carcinoma: pathogenesis, clinicopathologic and molecular biologic features, and diagnostic problems. Adv Anat Pathol. 2009;16:267–282. - PMC - PubMed
    1. Diaz-Padilla I, Malpica AL, Minig L, et al. Ovarian low-grade serous carcinoma: a comprehensive update. Gynecol Oncol. 2012;126:279–285. - PubMed
    1. McCluggage WG. The pathology of and controversial aspects of ovarian borderline tumours. Curr Opin Oncol. 2010;22:462–472. - PubMed
    1. Bonome T, Lee JY, Park DC, et al. Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary. Cancer Res. 2005;65:10602–10612. - PubMed

Publication types

MeSH terms

-