Yong W H, Chou D, Ueki K, Harsh G R, von Deimling A, Gusella J F, Mohrenweiser H W, Louis D N
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Charlestown 02129, USA.
J Neuropathol Exp Neurol. 1995 Sep;54(5):622-6. doi: 10.1097/00005072-199509000-00002.
Chromosome 19q harbors a tumor suppressor gene that is involved in astrocytoma, oligodendroglioma and mixed glioma tumorigenesis. We had previously mapped this gene to an approximately 5 megabase region of chromosome 19q13.2-13.3 between APOC2 and HRC. To narrow the location of this tumor suppressor further, we studied 138 gliomas for loss of allelic heterozygosity at six microsatellite polymorphisms between APOC2 and HRC, including a newly described polymorphism in the ERCC2 gene. Allelic loss occurred in 48 gliomas (35%), including 25 of 41 oligodendroglial tumors (61%). Four cases had proximal breakpoints within the APOC2-HRC region, two telomeric to ERCC2 and two telomeric to D19S219. In addition, one of the latter tumors had an interstitial deletion between D19S219 and D19S112, a distance of only 425 kilobases surrounding the DM (myotonic dystrophy) gene. These findings suggest that the glioma tumor suppressor on chromosome 19q maps to 19q13.3, telomeric to D19S219 and perhaps centromeric to D19S112. The data exclude a number of candidate genes from 19q13.2-13.3, including a putative phosphatase gene and the DNA repair/metabolism genes ERCC1, ERCC2 and probably LIG1.
19号染色体长臂包含一个肿瘤抑制基因，该基因参与星形细胞瘤、少突胶质细胞瘤和混合性胶质瘤的肿瘤发生过程。我们之前已将此基因定位到19号染色体长臂13.2 - 13.3区域的一个约5兆碱基的区间，位于载脂蛋白C2（APOC2）和组氨酸氨肽酶（HRC）之间。为了进一步缩小这个肿瘤抑制基因的定位范围，我们研究了138例胶质瘤，检测了APOC2和HRC之间6个微卫星多态性位点的等位基因杂合性缺失情况，其中包括在切除修复交叉互补基因2（ERCC2）基因中新发现的一个多态性位点。48例（35%）胶质瘤出现了等位基因缺失，其中41例少突胶质细胞瘤中有25例（61%）。4例在APOC2 - HRC区域内有近端断点，2例在ERCC2的端粒侧，2例在D19S219的端粒侧。此外，后一组肿瘤中的1例在D19S219和D19S112之间存在间质缺失，该区域距离强直性肌营养不良（DM）基因仅425千碱基。这些发现表明，19号染色体长臂上的胶质瘤肿瘤抑制基因定位于19q13.3，在D19S219的端粒侧，可能在D19S112的着丝粒侧。这些数据排除了19q13.2 - 13.3区域的多个候选基因，包括一个假定的磷酸酶基因以及DNA修复/代谢基因ERCC1、ERCC2，可能还有连接酶1（LIG1）。
