Wooten E C, Fults D, Duggirala R, Williams K, Kyritsis A P, Bondy M L, Levin V A, O'Connell P
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7750, USA.
Neuro Oncol. 1999 Jul;1(3):169-76. doi: 10.1093/neuonc/1.3.169.
Cancers that arise from astrocytes in the adult CNS present as either anaplastic astrocytomas (AAs) or as more aggressive glioblastomas multiforme (GBMs). GBMs either form de novo or progress from AAs. We proposed to examine the molecular genetic relationship between these CNS tumors by conducting a genome-wide allelic imbalance analysis that included 70 loci on examples of AA and GBM. We found significant loss of heterozygosity (LOH) at 13 discrete chromosomal loci in both AAs and GBMs. Loss was significant in both AAs and GBMs at 9 of these loci. AAs show the highest rates of LOH at chromosomes 1p, 4q, 6p, 9p, 11p, 11q, 13q, 14q, 15p, 17p, 17q, and 19q. GBMs showed the greatest losses at 1p, 6q, 8p, 9p, 10p, 10q, 11p, 13q, 17p, 17q, 18p, 18q, and 19q. GBMs also demonstrated significant amplification at the epidermal growth factor receptor locus (7p12). These data suggest that there are three classes of loci involved in glioma evolution. First are loci that are likely involved in early events in the evolution of both AAs and GBMs. The second class consists of AA-specific loci, typified by higher LOH frequency than observed in GBMs (4q, 6p, 17p, 17q, 19q). The third class consists of GBM-specific loci (6q, 8p, 10, 18q). Damage at these loci may either lead to de novo GBMs or permit existing AAs to progress to GBMs. Glioma-related LOH profiles may have prognostic implications that could lead to better diagnosis and treatment of brain cancer patients.
源自成人中枢神经系统星形胶质细胞的癌症表现为间变性星形细胞瘤（AA）或更具侵袭性的多形性胶质母细胞瘤（GBM）。GBM要么是原发性形成，要么是由AA进展而来。我们提议通过进行全基因组等位基因不平衡分析来研究这些中枢神经系统肿瘤之间的分子遗传关系，该分析涵盖了AA和GBM样本中的70个位点。我们在AA和GBM中均发现13个离散染色体位点存在显著的杂合性缺失（LOH）。在这些位点中的9个位点，AA和GBM中的缺失均很显著。AA在染色体1p、4q、6p、9p、11p、11q、13q、14q、15p、17p、17q和19q上显示出最高的LOH率。GBM在1p、6q、8p、9p、10p、10q、11p、13q、17p、17q、18p、18q和19q上显示出最大程度的缺失。GBM在表皮生长因子受体位点（7p12）也表现出显著扩增。这些数据表明，胶质瘤演变涉及三类位点。首先是可能参与AA和GBM演变早期事件的位点。第二类是AA特异性位点，其特征是LOH频率高于GBM（4q、6p、17p、17q、19q）。第三类是GBM特异性位点（6q、8p、10、18q）。这些位点的损伤可能导致原发性GBM的形成，或者使现有的AA进展为GBM。胶质瘤相关的LOH图谱可能具有预后意义，从而有助于改善脑癌患者的诊断和治疗。
