BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas

Abstract

Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.

Figure 1

Loss of heterozygosity (LOH) analysis of low-grade ovarian serous carcinoma with 50K SNP arrays. LOH regions were highlighted in blue color. Stars indicate Tumors with a KRAS mutation. SBOT, serous borderline ovarian tumor. LG/SBOT, low-grade serous tumor with adjacent serous borderline tumor. LG, low-grade serous tumor without adjacent serous borderline tumor.

Figure 2

Genes differentially expressed between serous borderline tumors with BRAF mutation (Braf) and serous borderline tumors without BRAF mutation (wt).