Chiariello E, Roz L, Albarosa R, Magnani I, Finocchiaro G
Istituto Nazionale Neurologico C Besta, Department of Biochemistry and Genetics, Milan, Italy.
Oncogene. 1998 Jan 29;16(4):541-5. doi: 10.1038/sj.onc.1201689.
A novel tumor suppressor, PTEN/MMAC1, was recently found on chromosome 10q23 and mutations of this gene were described in about 20% of primary glioblastomas (GBM) and 60% of GBM cell lines. To define further the relevance of PTEN/MMAC1 mutations in GBM we investigated by SSCP analysis its coding sequence in 44 gliomas, including 41 GBM, and in 21 short-term cultures (15 GBM and six malignant astrocytomas). Loss of heterozygosity (LOH) at 10q23 was present in at least one marker in the vicinity of the PTEN/MMAC1 locus in 59% of the informative GBM (primary tumors and cell cultures). SSCP variant bands were found in seven primary GBM (17%) and in one short-term GBM culture and sequence analysis confirmed the presence of somatic mutations in all these cases (five missense, one splicing mutation and two small deletions). These data indicate that PTEN/MMAC1 is inactivated in a subset of GBM and suggest that the high mutation frequency previously found in GBM established cell lines reflects culture condition artifacts rather than the true mutation frequency in vivo. Other suppressors, located on chromosome 10q, may also have a critical role in glioma tumorigenesis.
一种新的肿瘤抑制基因PTEN/MMAC1最近在染色体10q23上被发现，在大约20%的原发性胶质母细胞瘤（GBM）和60%的GBM细胞系中发现了该基因的突变。为了进一步明确PTEN/MMAC1突变在GBM中的相关性，我们通过单链构象多态性分析（SSCP）研究了44例胶质瘤（包括41例GBM）以及21个短期培养物（15例GBM和6例恶性星形细胞瘤）中的编码序列。在59%的信息性GBM（原发性肿瘤和细胞培养物）中，PTEN/MMAC1基因座附近至少有一个标记存在杂合性缺失（LOH）。在7例原发性GBM（17%）和1例短期GBM培养物中发现了SSCP变异条带，序列分析证实所有这些病例中均存在体细胞突变（5个错义突变、1个剪接突变和2个小缺失）。这些数据表明，PTEN/MMAC1在一部分GBM中失活，提示先前在GBM建立的细胞系中发现的高突变频率反映的是培养条件造成的假象，而非体内的真实突变频率。位于染色体10q上的其他抑制基因可能在胶质瘤的肿瘤发生中也起关键作用。
