Mutational status of KRAS, NRAS, and BRAF in primary clear cell ovarian carcinoma

Abstract

Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer with characteristic biological features and aggressive clinical behavior. OCCCs show a pattern of gene mutations different from other type I ovarian malignancies, notably a higher frequency of PIK3CA mutations. In low grade serous ovarian cancer, KRAS and BRAF mutations are frequent, but little data are available on the mutational status of these genes in OCCCs. To clarify this issue, we designed a clinicopathological study with the aim to establish the incidence of KRAS, NRAS, and BRAF hot spot mutations in OCCC. Between December 2006 and June 2012, 22 patients with a proven diagnosis of OCCC were admitted to our Institutions. In all cases, final diagnosis was established according to FIGO and WHO criteria. All women received complete surgical staging. The PyroMark Q24 system (Qiagen GmbH, Hilden, Germany) was used for pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions on 2.5-μm sections of formalin-fixed paraffin-embedded tissue from primary OCCC. Pyrosequencing analysis of KRAS, NRAS, and BRAF hot spot regions revealed the presence of mutations only at codon 12 in exon 2 of KRAS in 3 of 22 (14 %) cases. We found no mutations in the hot spot regions of NRAF (exons 2, 3, 4) or BRAF (exon 15). The median age of women with a KRAS mutated OCCC was 74 years. These OCCC were unilateral FIGO stage IA lesions in two cases associated with foci of endometriosis. We conclude that in 14 % of OCCCs, a KRAS mutation occurs in codon 2 exon 2. NRAS and BRAF mutations were not found.

Molecular status ofPI3KCA,KRASandBRAFin ovarian clear cell carcinoma: an analysis of 63 patients

“…The present study confirms the absence of BRAF mutations, underling once again that BRAF alterations are a very rare event and that the PI3K/AKT pathway is the principal pathway for carcinogenesis and progression, for this kind of ovarian tumour 19. This is in line with the data presented by Singer et al and Dodds et al 9 39.…”

“…Few and contrasting data have been reported, until now, regarding mutational status of KRAS . We found a lower percentage of KRAS hotspot mutations (8/63; 13%) in 63 patients with OCCC compared with PI3KCA hotspot mutations (20/63; 32%), but in line with our previous study 19. Our percentage of KRAS hotspot mutations in OCCC is higher than that of 4.7% found by Jones et al in their study, but in line with that showed in a recent study of 69 patients with OCCC analysed by next generation sequencing, where KRAS was found altered in 11% of cases 16 36.…”

Frequency of RAS Mutations (KRAS, NRAS, HRAS) in Human Solid Cancer

“…KRAS mutation is 0% to 5% in non-endometrioid endometrial cancers. [46][47][48][49][50][51][52][53][54][55][56] The frequency of KRAS mutations in cervical cancer ranges between 5% and 14%. In the United States, the frequency of KRAS mutation is 8.8% in patients with cervical cancer.…”

Involvement of Chromatin Remodeling Genes and the Rho GTPases RhoB and CDC42 in Ovarian Clear Cell Carcinoma

“…The variant pattern revealed a heterogeneous mutational landscape, but is largely in line with what has previously been reported. The oncogene KRAS is often mutated in low proliferating, type 1 ovarian tumors (23). A single KRAS variant was found in our cohort, in line with the previously reported overall variant frequency of 7–14% in OCCC (21, 23).…”