Mutation of NRAS is a rare genetic event in ovarian low-grade serous carcinoma

• Published in: Human pathology Vol. 68; pp. 87 - 91
• Main Authors: Xing, Deyin, Suryo Rahmanto, Yohan, Zeppernick, Felix, Hannibal, Charlotte G., Kjaer, Susanne K., Vang, Russell, Shih, Ie-Ming, Wang, Tian-Li
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2017; Elsevier Limited
• Subjects: Adult; Age; Aged; Aged, 80 and over; Archives & records; Baltimore; Biomarkers, Tumor - genetics; Carcinoma - genetics; Carcinoma - pathology; Cell Proliferation; Denmark; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; Female; Genetic Predisposition to Disease; GTP Phosphohydrolases - genetics; Humans; Low-grade serous carcinoma; Membrane Proteins - genetics; Middle Aged; Mutation; Mutation Rate; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Neoplasms, Cystic, Mucinous, and Serous - genetics; Neoplasms, Cystic, Mucinous, and Serous - pathology; NRAS mutation; Oncogenic driver; Ovarian cancer; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Pathology; Patients; Phenotype; Polymerase chain reaction; Proto-Oncogene Proteins B-raf - genetics; RAS signaling; Studies; Tumors; Young Adult; NRAS mutation; Low-grade serous carcinoma; Oncogenic driver; RAS signaling; Ovarian cancer
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2017.08.021

Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of SBT to invasive low-grade serous carcinoma (LGSC) remains largely unknown. Although mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression. In this study, we analyzed NRAS exon 3 mutational status in 98 cases that were diagnosed with SBT/atypical proliferative serous tumor, noninvasive LGSC, or invasive LGSC. Of the latter, NRAS Q61R (CAA to CGA) mutations were detected in only 2 of 56 (3.6%) cases. The same mutation was not detected in any of the SBTs (atypical proliferative serous tumors) or noninvasive LGSCs. Mutational analysis for hotspots in KRAS and BRAF demonstrated a wild-type pattern of KRAS and BRAF in one of the NRAS-mutated cases. Interestingly, another LGSC case with NRAS mutation harbored a concurrent BRAF V600L mutation. These findings indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC. Further studies to identify other oncogenic events that drive LGSC progression are warranted. •NRAS mutation is postulated to facilitate the development of low-grade serous carcinoma (LGSC).•NRAS hotspot (Q61R) mutation was detected in only 3.6% cases of LGSCs in this study.•Low prevalence of mutation indicates that NRAS plays a limited role in the development of LGSC.