Ludwig Center for Cancer Genetics and Howard Hughes Medical Institutions, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
Science. 2011 Sep 9;333(6048):1453-5. doi: 10.1126/science.1210557. Epub 2011 Aug 4.
Oligodendrogliomas are the second most common malignant brain tumor in adults and exhibit characteristic losses of chromosomes 1p and 19q. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven tumors. Among other changes, we found that the CIC gene (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six cases and that the FUBP1 gene [encoding far-upstream element (FUSE) binding protein] on chromosome 1p was somatically mutated in two tumors. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.
少突胶质细胞瘤是成人中第二常见的恶性脑肿瘤，表现为特征性的 1p 和 19q 染色体缺失。为了确定这种改变的分子遗传基础，我们对 7 个肿瘤进行了外显子组测序。除其他改变外，我们发现 19q 染色体上的 CIC 基因（果蝇 capicua 基因的同源物）在 6 例中发生了体细胞突变，而 1p 染色体上的 FUBP1 基因（编码远上游元件（FUSE）结合蛋白）在 2 个肿瘤中发生了体细胞突变。对另外 27 例少突胶质细胞瘤的检测显示，CIC 和 FUBP1 的突变分别出现在 12 例和 3 例肿瘤中，其中 58%的突变预计会导致编码蛋白的截断。这些结果表明这些基因在少突胶质细胞的生物学和病理学中具有关键作用。
