Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
Service d'Oncologie Médicale, Sarcoma center, Netsarc National Network, Hôpital Cochin, Hôpitaux Universitaires Paris Centre, Assistance Publique-Hôpitaux de Paris, Paris, France.
J Med Genet. 2020 Feb;57(2):104-108. doi: 10.1136/jmedgenet-2018-105594. Epub 2018 Oct 23.
Rhabdomyosarcoma (RMS) is rare cancer affecting children and adults. Pleomorphic RMS histology is almost exclusive to adult patients and often resistant to chemotherapy.
We report the case of a 19-year-old patient who presented with a metastatic chemoresistant pleomorphic RMS.
Considering the poor prognosis and the few systemic therapeutic options, we decided to carry out a whole exome sequencing (WES) of the tumour and germline DNA.
WES identified a germline variation (c.1863_1864insT) in the gene corresponding to a pathogenic mutation: (p. Leu622Serfs*10), whereas the family history did not fit with classical criteria for Lynch syndrome. Loss-of-heterozygosity at locus was found in the tumour. Immunohistochemistry showed loss of MLH1 and PMS2 nuclear expression in the tumour cells. In view of the mismatch repair defects and a high programmed cell death ligand 1 (PD-L1) expression (60% of tumour cells expressed PD-L1), we administrated an anti-PD-1 antibody to the patient. He achieved a rapid complete response of the lung metastases, which appears sustained after a 1-year follow-up.
This observation of an RMS revealing an unexpected Lynch syndrome underlines the overlap between tumorous and germline molecular genetics and emphasises the major impact of cancer genomic medicine in clinical practice for guiding treatment decision.
横纹肌肉瘤（RMS）是一种罕见的癌症，影响儿童和成人。多形性 RMS 组织学几乎仅见于成年患者，且常对化疗有抗性。
我们报告了一例 19 岁转移性耐药多形性 RMS 患者的病例。
鉴于预后较差且系统治疗选择有限，我们决定对肿瘤和种系 DNA 进行全外显子组测序（WES）。
WES 鉴定出一个基因的种系变异（c.1863_1864insT），对应一个致病性突变：（p.Leu622Serfs*10），而家族史不符合经典的林奇综合征标准。在肿瘤中发现了 基因座的杂合性丢失。免疫组化显示肿瘤细胞中 MLH1 和 PMS2 核表达缺失。鉴于错配修复缺陷和高水平的程序性细胞死亡配体 1（PD-L1）表达（60%的肿瘤细胞表达 PD-L1），我们给患者施用了一种抗 PD-1 抗体。他的肺部转移瘤迅速完全缓解，在 1 年随访后仍持续缓解。
该 RMS 观察结果揭示了一种出乎意料的林奇综合征，突显了肿瘤和种系分子遗传学之间的重叠，并强调了癌症基因组医学在指导治疗决策方面对临床实践的重大影响。
