Université Paris Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Mol Med. 2011 Jan-Feb;17(1-2):79-87. doi: 10.2119/molmed.2010.00079. Epub 2010 Sep 10.
Patients with NF1 microdeletion develop more neurofibromas at a younger age, and have an increased risk of malignant peripheral nerve sheath tumors (MPNSTs). We postulated that the increased risk of malignancy could be due to inactivation, in addition to NF1, of a second tumor suppressor gene located in the typical 1.4-Mb microdeletion found in most of the microdeleted patients. We investigated the expression of NF1, the other 16 protein-coding genes and the 2 microRNAs located in the 1.4-Mb microdeletion by means of real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) in a large series of human dermal and plexiform neurofibromas and MPNSTs. Five genes were significantly upregulated: OMG and SUZ12 in plexiform neurofibromas and ATAD5, EVI2A and C17orf79 in MPNSTs. More interestingly, two genes were significantly downregulated (RNF135 and CENTA2) in tumor Schwann cells from MPNST biopsies and in MPNST cell lines. This study points to the involvement of several genes (particularly RNF135 and CENTA2) in the increased risk of malignancy observed in NF1-microdeleted patients.
NF1 微缺失患者在更年轻时出现更多神经纤维瘤，并且恶性外周神经鞘瘤 (MPNST) 的风险增加。我们推测，这种恶性肿瘤的风险增加可能是由于除 NF1 之外，位于大多数微缺失患者中发现的典型 1.4Mb 微缺失中的第二个肿瘤抑制基因失活所致。我们通过实时定量逆转录聚合酶链反应 (RT-PCR) 研究了位于 1.4Mb 微缺失中的 NF1、其他 16 个编码蛋白基因和 2 个 microRNA 在大量人真皮神经纤维瘤和 MPNST 中的表达。五个基因显著上调：丛状神经纤维瘤中的 OMG 和 SUZ12 以及 MPNST 中的 ATAD5、EVI2A 和 C17orf79。更有趣的是，两个基因在 MPNST 活检和 MPNST 细胞系中的肿瘤施万细胞中显著下调（RNF135 和 CENTA2）。这项研究表明，几个基因（特别是 RNF135 和 CENTA2）参与了 NF1 微缺失患者观察到的恶性肿瘤风险增加。
