*Department of Genome Analysis, Academic Medical Center ∥Department of Pathology, VU University Medical Center, Amsterdam §Department of Pathology, Nijmegen Center for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands †Institute for Human Genetics, University Hospital Muenster, Muenster ‡Institute for Neuropathology, Evangelisches Krankenhaus, Bielefeld, Germany.
Am J Surg Pathol. 2014 Mar;38(3):421-5. doi: 10.1097/PAS.0000000000000110.
Germline SMARCB1 mutations predispose in schwannomatosis patients to the development of multiple benign schwannomas and, in some cases, meningiomas. Here, we report on a 34-year-old female patient who developed multiple schwannomas at various locations and in addition a leiomyoma of the cervix uteri. She carried a c.362+1G>A mutation that inactivates the donor splice site of exon 3. This mutation caused the schwannomatosis phenotype in this patient and was also demonstrated to be present in her affected mother. The leiomyoma displayed the genetic features that are characteristic for germline SMARCB1 mutation-associated tumors. The mutant allele retained in the tumor, whereas the wild-type allele was lost by loss of heterozygosity. Furthermore, the loss of heterozygosity involved net loss of chromosome 22. An NF2 mutation was not found. However, quantitative polymerase chain reaction suggested that both NF2 copies were lost in the tumor. Immunostaining with a SMARCB1 antibody revealed the mosaic expression pattern that is typical for schwannomatosis-associated tumors. To our knowledge, this is the first reported case of leiomyoma associated with a germline SMARCB1 mutation. As such, it widens the spectrum of benign tumors associated with a germline SMARCB1 mutation.
胚系 SMARCB1 突变使神经鞘瘤病患者易患多发性良性神经鞘瘤，在某些情况下还易患脑膜瘤。在此，我们报告了一名 34 岁的女性患者，她在不同部位患有多个神经鞘瘤，此外还患有宫颈平滑肌瘤。她携带 c.362+1G>A 突变，使外显子 3 的供体位点失活。该突变导致该患者出现神经鞘瘤病表型，并且还在其受累的母亲中存在。平滑肌瘤显示出与胚系 SMARCB1 突变相关肿瘤的遗传特征。在肿瘤中保留了突变等位基因，而杂合性丢失导致 22 号染色体的净丢失。未发现 NF2 突变。然而，定量聚合酶链反应表明肿瘤中两个 NF2 拷贝均丢失。用 SMARCB1 抗体进行免疫染色显示出典型的神经鞘瘤病相关肿瘤的镶嵌表达模式。据我们所知，这是首例与胚系 SMARCB1 突变相关的平滑肌瘤病例。因此，它拓宽了与胚系 SMARCB1 突变相关的良性肿瘤谱。
