Rare-type mutations of MMAC1 tumor suppressor gene in human glioma cell lines and their tumors of origin

A total of 10 glioma cell lines were examined to evaluate the status of the MMAC1 gene, a candidate tumor suppressor gene, Six cell lines showed mutat ions with presumed loss of heterozygosity and 1 cell line showed no mRNA ex pression, The 6 mutations consisted of 3 3-bp deletions (codons 17, 101 or 199), 1 missense mutation (codon 252) and 2 truncation mutations (1 nonsens e mutation at codon 233 and 1 2-bp insertion at codon 241), Among them, the 3-bp deletions, which are a rare type of mutation in MMAC1 gene, were loca ted in the N-terminal half (codons 1-212) of the coding region, which is co nsidered important in MMAC1 function, The missense mutation was located unu sually in the C-terminal half (codons 212-403), but it was in a small regio n in which some other reported missense mutations are clustered. Thus, thes e 4 mutations were suggested to have functional effects on the MMAC1 activi ty, like the other 2 mutations with predicted protein truncations, By seque nce analysis of cDNA clones, we confirmed that all the mutations including these 4 rare ones were in the MMAC1 gene, not in the PTH2 pseudogene, in 2 cases, we also examined the primary glioma tissues from which the cell line s had been derived and found the same mutations as in the cell lines in bot h eases, This suggested that the mutations in these cell lines were derived from the primary glioma tissues, but not from artifacts arising during lon g-term in vitro cultivation.