公开(公告)号：US09873917B2

公开(公告)日：2018-01-23

申请号：US14233296

申请日：2012-07-18

申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Chetan Bettegowda ,  Nishant Agrawal ,  Nickolas Papadopoulos ,  Darell Bigner ,  Hai Yan ,  Roger McLendon

发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Chetan Bettegowda ,  Nishant Agrawal ,  Nickolas Papadopoulos ,  Darell Bigner ,  Hai Yan ,  Roger McLendon

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/156 ,  C12Q2600/158

摘要： Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. 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.

公开(公告)号：US20140221219A1

公开(公告)日：2014-08-07

申请号：US14233296

申请日：2012-07-18

申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Chetan Bettegowda ,  Nishant Agrawal ,  Nickolas Papadopoulos ,  Darell Bigner ,  Hai Yan ,  Roger Mclendon

发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Chetan Bettegowda ,  Nishant Agrawal ,  Nickolas Papadopoulos ,  Darell Bigner ,  Hai Yan ,  Roger Mclendon

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/156 ,  C12Q2600/158

摘要： Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. 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.

摘要翻译： 少突神经胶质瘤是成人中第二常见的恶性脑肿瘤。 这些肿瘤通常包含染色体异常，涉及染色体1和染色体1的致晕体融合，导致前者的整个短臂和后者的长臂的损失。 为了确定这种改变的分子遗传基础，我们对染色体1p和19q损失进行了7个分离性少突胶质细胞瘤的外切测序。 在其他变化中，我们发现在七种病例中的六种中，染色体19q上的CIC（果蝇基因capicua的同系物）被体细胞突变，并且染色体1p上的FUBP1（远上游元件（FUSE）结合蛋白）在两个体内被突变 的七例。 另外27例少突胶质细胞瘤的检查显示有12例和3例分别具有CIC和FUBP1突变的肿瘤，其中58％预计会导致编码蛋白的截短。 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的关键作用。