Mehine Miika, Khamaiseh Sara, Ahvenainen Terhi, Heikkinen Tuomas, Äyräväinen Anna, Pakarinen Päivi, Härkki Päivi, Pasanen Annukka, Bützow Ralf, Vahteristo Pia
Applied Tumor Genomics Research Program, University of Helsinki, 00014 Helsinki, Finland.
Department of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland.
Cancers (Basel). 2020 Dec 19;12(12):3839. doi: 10.3390/cancers12123839.
Uterine leiomyomas are benign smooth muscle tumors occurring in 70% of women of reproductive age. The majority of leiomyomas harbor one of three well-established genetic changes: a hotspot mutation in , overexpression of , or biallelic loss of . The majority of studies have classified leiomyomas by complex and costly methods, such as whole-genome sequencing, or by combining multiple traditional methods, such as immunohistochemistry and Sanger sequencing. The type of specimens and the amount of resources available often determine the choice. A more universal, cost-effective, and scalable method for classifying leiomyomas is needed. The aim of this study was to evaluate whether RNA sequencing can accurately classify formalin-fixed paraffin-embedded (FFPE) leiomyomas. We performed 3'RNA sequencing with 44 leiomyoma and 5 myometrium FFPE samples, revealing that the samples clustered according to the mutation status of , , and . Furthermore, we confirmed each subtype in a publicly available fresh frozen dataset. These results indicate that a targeted 3'RNA sequencing panel could serve as a cost-effective and robust tool for stratifying both fresh frozen and FFPE leiomyomas. This study also highlights 3'RNA sequencing as a promising method for studying the abundance of unexploited tissue material that is routinely stored in hospital archives.
子宫平滑肌瘤是一种良性平滑肌肿瘤，在70%的育龄女性中出现。大多数平滑肌瘤存在三种已明确的基因变化之一： 中的热点突变、 的过表达或 的双等位基因缺失。大多数研究通过复杂且昂贵的方法（如全基因组测序）或通过结合多种传统方法（如免疫组织化学和桑格测序）对平滑肌瘤进行分类。标本类型和可用资源量通常决定了分类方法的选择。因此，需要一种更通用、经济高效且可扩展的平滑肌瘤分类方法。本研究的目的是评估RNA测序是否能准确分类福尔马林固定石蜡包埋（FFPE）的平滑肌瘤。我们对44例平滑肌瘤和5例子宫肌层FFPE样本进行了3'RNA测序，结果显示样本根据 、 和 的突变状态聚类。此外，我们在一个公开可用的新鲜冷冻数据集中证实了每种亚型。这些结果表明，靶向3'RNA测序面板可作为一种经济高效且强大的工具，用于对新鲜冷冻和平滑肌瘤FFPE进行分层。本研究还强调了3'RNA测序是一种很有前景的方法，可用于研究医院档案中常规存储的未充分利用的组织材料的丰度。
