Fohlen Martine, Harzallah Ines, Polivka Marc, Giuliano Fabienne, Pons Linda, Streichenberger Nathalie, Dorfmüller Georg, Touraine Renaud
Service de neurochirurgie pediatrique, Foundation Rothschild Hospital, Paris, France.
Service de Génétique Clinique, Chromosomique et Moléculaire, Centre de Compétence des Epilepsies rares (CReER), CHU-Hôpital Nord, Saint Etienne, France.
Childs Nerv Syst. 2020 May;36(5):961-965. doi: 10.1007/s00381-020-04551-4. Epub 2020 Feb 26.
Subependymal giant-cell astrocytomas (SEGAs) are low grade intraventricular tumors typically found in patients with tuberous sclerosis complex (TSC). The occurrence of SEGA in non TSC patients is very rare and from a genetic point of view these so-called solitary SEGA are thought to result either from somatic mutations in one of the TSC genes (TSC1 or TSC2) limited to the tumor, or be part of a "forme fruste" of TSC with somatic mosaicism. We report on three new cases of solitary SEGA with germline and somatic mutation analysis.
We retrospectively analyzed TSC genes in three patients with a solitary SEGA using next-generation sequencing technique.
In the three patients, a somatic mutation of TSC1 or TSC2 was found only in the tumor cells: one patient had a TSC1 heterozygote mutation, involving the natural acceptor splicing site of intron 15 (c.1998-1G > A (p.?). Two patients had a TSC2 mutation located in the canonical splicing donor site of intron 5 (c.599 + 1G > A) in 70% of the alleles in one patient and in exon 9: c.949_955dup7 (p.V319DfxX21) in 25 of the alleles in the second patient. No other TSC mutations were found in patient's blood or tumor and those identified mutations were absent in blood DNA from parents and siblings.
We therefore conclude that solitary SEGA can occur with a TSC1 or TSC2 mutation limited to the tumor in patients without TSC.
室管膜下巨细胞星形细胞瘤（SEGA）是一种低级别的脑室内肿瘤，常见于结节性硬化症（TSC）患者。非TSC患者中SEGA的发生极为罕见，从遗传学角度来看，这些所谓的孤立性SEGA被认为要么是由于TSC基因（TSC1或TSC2）之一仅限于肿瘤的体细胞突变所致，要么是TSC“顿挫型”伴有体细胞镶嵌现象的一部分。我们报告3例新的孤立性SEGA病例并进行种系和体细胞突变分析。
我们采用下一代测序技术对3例孤立性SEGA患者的TSC基因进行了回顾性分析。
在这3例患者中，仅在肿瘤细胞中发现了TSC1或TSC2的体细胞突变：1例患者有TSC1杂合子突变，涉及内含子15的天然受体剪接位点（c.1998-1G＞A（p.?））。2例患者有TSC2突变，1例患者70%的等位基因中位于内含子5的经典剪接供体位点（c.599+1G＞A），另1例患者25个等位基因中位于外显子9：c.949_955dup7（p.V319DfxX21）。在患者的血液或肿瘤中未发现其他TSC突变，且在父母和兄弟姐妹的血液DNA中也未发现所鉴定的突变。
因此，我们得出结论，孤立性SEGA可发生于无TSC的患者，其TSC1或TSC2突变仅限于肿瘤。
