Rosso S M, van Dekken H, Krishnadath K K, Alers J C, Kros J M
Department of Pathology, University Hospital Rotterdam, The Netherlands.
J Neuropathol Exp Neurol. 1997 Oct;56(10):1125-31. doi: 10.1097/00005072-199710000-00006.
Recently, lineage-specific genetic pathways of tumor progression have been suggested in both oligodendrogliomas and astrocytomas. Aberrations consistently reported in gliomas include chromosomes 1, 7, 10, 17 and 19. Identification of specific genetic damage may have important clinical consequences, because oligodendrogliomas, unlike astrocytomas, are responsive to chemotherapy. Genetic alterations specific for tumor type and tumor progression were investigated in 5 pairs of recurrent astrocytomas and 8 pairs of recurrent oligodendrogliomas by means of interphase in situ hybridization (ISH) to paraffin-embedded, formalin-fixed tissue sections. A set of DNA probes specific for the centromeric regions of chromosomes 1, 7, 10, 17, X and Y was applied. Since LOH studies on oligodendrogliomas have revealed losses in the region of 1p32-1p36, a DNA probe specific for the 1p36.3 locus was included. Hybridization with the 1p36.3 probe revealed loss of 1p in 5 of the 8 oligodendroglioma recurrences, the aberration being present in the primary tumors in 2 cases. In none of the astrocytomas was loss of 1p observed. Numerical aberrations were found in one astrocytoma pair (+7) and in the second biopsy of an oligodendroglioma (+7, -10). Aneuploidy was found by in situ hybridization in 8 of the 13 tumor pairs. Detection of aberrations in the 1p36.3 locus by interphase in situ hybridization to paraffin-embedded, formalin-fixed tumors may become a very useful tool in delineation of oligodendroglial from astrocytic genotypes, directing tumor specific therapy. The technique may be of crucial importance in tumor cases in which histologic criteria of lineage are not obvious.
最近,在少突胶质细胞瘤和星形细胞瘤中均已提出肿瘤进展的谱系特异性遗传途径。胶质瘤中一致报道的畸变包括1、7、10、17和19号染色体。识别特定的基因损伤可能具有重要的临床意义,因为与星形细胞瘤不同,少突胶质细胞瘤对化疗有反应。通过对石蜡包埋、福尔马林固定的组织切片进行间期原位杂交(ISH),研究了5对复发性星形细胞瘤和8对复发性少突胶质细胞瘤中肿瘤类型和肿瘤进展的特异性基因改变。应用了一组针对1、7、10、17、X和Y号染色体着丝粒区域的DNA探针。由于对少突胶质细胞瘤的杂合性缺失(LOH)研究显示1p32 - 1p36区域存在缺失,因此纳入了一个针对1p36.3位点的DNA探针。与1p36.3探针杂交显示,在8例少突胶质细胞瘤复发中有5例存在1p缺失,其中2例在原发肿瘤中就已存在这种畸变。在星形细胞瘤中均未观察到1p缺失。在一对星形细胞瘤中发现了数值畸变(+7),在一例少突胶质细胞瘤的第二次活检中发现了数值畸变(+7,-10)。通过原位杂交在13对肿瘤中有8对发现了非整倍体。通过对石蜡包埋、福尔马林固定的肿瘤进行间期原位杂交检测1p36.3位点的畸变,可能成为区分少突胶质细胞型与星形细胞型基因型、指导肿瘤特异性治疗的非常有用的工具。该技术在谱系的组织学标准不明显的肿瘤病例中可能至关重要。