BACKGROUND: Low-grade serous ovarian cancer (LGSOC) is a rare subtype of epithelial ovarian carcinoma. Limited data regarding the molecular-genetic background exist beyond mutations in the RAS signaling pathway. There is a growing need to better characterize these tumors due to chemoresistance and limited therapeutic options in advanced or recurrent disease. METHODS: We performed genome-wide copy number aberration (CNA) profiles and mutation hotspot screening (KRAS, BRAF, NRAS, ERBB2, PIK3CA, TP53) in 38 LGSOC tumor samples. RESULTS: We detected mutations in the RAS-signaling pathway in 36.8% of cases, including seven KRAS, four BRAF, and three NRAS mutations. We identified two mutations in PIK3CA and one mutation in MAP3K1, EGFR, and TP53. CNAs were detected in 86.5% of cases. None of the focal aberrations was correlated with specific clinical characteristics. The most frequently detected CNA was loss of 1p36.33 in 54.1% of cases, with a trend towards lower progression-free survival and overall survival in patients with 1p36.33 loss. CONCLUSIONS: Activating RAS mutations were dominant in our series, with supplementary detection of two PIK3CA mutations which may lead to therapeutic options. Furthermore, we detected 1p36.33 deletions in half of the cases, indicating a role in tumorigenesis, and these deletions may serve as a prognostic marker.

背景：低度浆液性卵巢癌（LGSOC）是上皮性卵巢癌的一种罕见亚型。关于分子遗传背景的有限数据存在于RAS信号通路中的突变之外。由于在晚期或复发性疾病中的化学抗性和有限的治疗选择，越来越需要更好地表征这些肿瘤。方法：我们在38个LGSOC肿瘤样本中进行了全基因组拷贝数畸变（CNA）概况和突变热点筛选（KRAS，BRAF，NRAS，ERBB2，PIK3CA，TP53）。结果：在36.8％的病例中，我们检测到RAS信号通路中的突变，包括7个KRAS，4个BRAF和3个NRAS突变。我们在PIK3CA中发现了两个突变，在MAP3K1，EGFR和TP53中发现了一个突变。在86.5％的病例中检测到CNA。没有一个像差与特定的临床特征相关。在54.1％的病例中，最常检测到的CNA是1p36.33的丢失，而在1p36.33丢失的患者中，无进展生存率和总体生存率都有降低的趋势。结论：激活的RAS突变在我们的系列中占主导地位，补充检测到两个PIK3CA突变，这可能导致治疗选择。此外，我们在一半的病例中检测到1p36.33缺失，表明其在肿瘤发生中起作用，这些缺失可作为预后标记。