Chemoresistant pleomorphic rhabdomyosarcoma: whole exome sequencing reveals underlying cancer predisposition and therapeutic options
Chemoresistant pleomorphic rhabdomyosarcoma: whole exome sequencing reveals underlying cancer predisposition and therapeutic options
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耐药多形性横纹肌肉瘤：全外显子组测序揭示潜在的癌症易感性和治疗选择
DOI：
10.1136/jmedgenet-2018-105594
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发表时间：
2020-02-01
影响因子：
4
通讯作者：
Laurent-Puig, Pierre
中科院分区：
文献类型：
--
作者：
Tlemsani, Camille;Leroy, Karen;Laurent-Puig, Pierre
横纹肌肉瘤（RMS）是一种罕见的癌症，影响儿童和成人。多形性横纹肌肉瘤组织学几乎是唯一的成年患者，往往耐化疗。目的我们报告的情况下，19岁的病人谁提出了转移化疗耐药多形性横纹肌肉瘤。方法考虑到预后差，很少有系统的治疗选择，我们决定对肿瘤和生殖系DNA进行全外显子组测序（WES）。结果WES鉴定出一个生殖系变异（c.1863_1864insT）在MLH 1基因中对应于致病性突变：（p.Leu622Serfs *10），而家族史不符合Lynch综合征的经典标准。MLH 1位点的杂合性丢失被发现在肿瘤。免疫组化显示肿瘤细胞中MLH 1和PMS 2核表达缺失。鉴于错配修复缺陷和高程序性细胞死亡配体1（PD-L1）表达（60%的肿瘤细胞表达PD-L1），我们向患者施用抗PD-1抗体。他实现了快速完全反应的肺转移，这似乎持续了1年的后续up.Conclusion这一观察RMS揭示了一个意想不到的林奇综合征强调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临床实践中的重大影响，指导治疗决策。
Background Rhabdomyosarcoma (RMS) is rare cancer affecting children and adults. Pleomorphic RMS histology is almost exclusive to adult patients and often resistant to chemotherapy.Objective We report the case of a 19-year-old patient who presented with a metastatic chemoresistant pleomorphic RMS.Methods 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.Results WES identified a germline variation (c.1863_1864insT) in the MLH1 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 MLH1 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.Conclusion 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.