Seryakov Alexander, Magomedova Zaynab, Suntsova Maria, Prokofieva Anastasia, Rabushko Elizaveta, Glusker Alexander, Makovskaia Lyudmila, Zolotovskaia Marianna, Buzdin Anton, Sorokin Maxim
Medical Holding SM-Clinic, Moscow, Russia.
The Laboratory of Clinical and Genomic Bioinformatics, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
Front Oncol. 2021 Aug 30;11:666001. doi: 10.3389/fonc.2021.666001. eCollection 2021.
Uterine leiomyosarcoma (UL) is a rare malignant tumor that develops from the uterine smooth muscle tissue. Due to the low frequency and lack of sufficient data from clinical trials there is currently no effective treatment that is routinely accepted for UL. Here we report a case of a 65-years-old female patient with metastatic UL, who progressed on ifosfamide and doxorubicin therapy and developed severe hypertensive crisis after administration of second line pazopanib, which lead to treatment termination. Rapid progression of the tumor stressed the need for the alternative treatment options. We performed RNA sequencing and whole exome sequencing profiling of the patient's biopsy and applied Oncobox bioinformatic algorithm to prioritize targeted therapeutics. No clinically relevant mutations associated with drug efficiencies were found, but the Oncobox transcriptome analysis predicted regorafenib as the most effective targeted treatment option. Regorafenib administration resulted in a complete metabolic response which lasted for 10 months. In addition, RNA sequencing analysis revealed a novel cancer fusion transcript of gene with fusion partner Several chimeric transcripts for and genes were previously found in uterine neoplasms and some of them were associated with tumor prognosis. However, their combination was detected in this study for the first time. Taken together, these findings evidence that RNA sequencing may complement analysis of clinically relevant mutations and enhance management of oncological patients by suggesting putative treatment options.
子宫平滑肌肉瘤（UL）是一种罕见的恶性肿瘤，起源于子宫平滑肌组织。由于其发病率低且缺乏来自临床试验的足够数据，目前尚无常规接受的有效治疗方法用于UL。在此，我们报告一例65岁转移性UL女性患者，其在接受异环磷酰胺和阿霉素治疗后病情进展，在给予二线药物帕唑帕尼后发生严重高血压危象，导致治疗终止。肿瘤的快速进展凸显了需要其他治疗选择。我们对患者的活检组织进行了RNA测序和全外显子测序分析，并应用Oncobox生物信息算法对靶向治疗药物进行优先级排序。未发现与药物疗效相关的临床相关突变，但Oncobox转录组分析预测瑞戈非尼是最有效的靶向治疗选择。给予瑞戈非尼后产生了持续10个月的完全代谢反应。此外，RNA测序分析揭示了一个与融合伴侣基因的新型癌症融合转录本。先前在子宫肿瘤中发现了几个与基因和基因相关的嵌合转录本，其中一些与肿瘤预后相关。然而，本研究首次检测到它们的组合。综上所述，这些发现证明RNA测序可能补充临床相关突变分析，并通过提出假定的治疗选择来加强肿瘤患者的管理。
