Point mutations leading to the activation of ras genes represent one of the best-studied mechanisms that convert porto-onocogenes into transforming sequences. The human ras gens family comprises 3 active members. H-ras, K-ras and N-ras, and a
growing
list of distantly related genes. The 21-kDa ras proteins are located at the inner surface of the plasma memberane, bind guanine nucleotides and possess intrinsic GTPase activity. although the precise physiological fuction of ras-encoded proteins
remains
to be elucidated, it appears that they are involved in transduction of receptor-mediated external signals across the cell membrane.
The incidence of ras gene mutations varies among different kinds of tumors. The highest incidence of ras gene mutations was reported in pancreatic adenocarcinomas, where about 90% of the tumors showed a mutant K-ras gene. In addition, despite
several
possible sites of mutation in the ras genes, the mutations found to date have been restricted in codon 12 of the K-ras gene in pancreatic adenocarcinoma. However there have been no report on ras gene mutation of the pancreatic tumor in Korea.
To evaluate the trequency of K-ras gene mutations, we analyzed the paraffin-embedded sections obtained from 6 cases of pancreatic adenocarcinoma, 3 cases of mucinous cystadenoma (including mucin-secreting ductectatic type of mucinous cystadenoma)
and 1
case of mucinous cystadenocar cinoma by in vitro amplification of target sequences via polymerase chain reaction and selective oligonucleotide hybridization. Specific point mutation at K-ras codon 12 was found in 1 of 6 cases of pancreastic
cancer.
The
point mutation was a G-to-A transition at the second base (aspartic acid substitution). No mutations were found in all cases with mucinous cystadenoma, mucinous cystadenocarcinoma and adjacent normal pancreatic tissues.
We might conclude that K-ras activation at codon 12 might be related to the pancreas cancer but a more extensive analysis including direct sequencing at codon 12, 13 and 61 will be required to determine whether there are correlations of
pancreatic
cancer with point mutations or not.
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