Van Den Broek M H, Renault B, Fodde R, Verspaget H, Griffioen G, Khan P M
MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University, The Netherlands.
Anticancer Res. 1993 May-Jun;13(3):587-92.
An unselected series of colorectal adenocarcinomas together with their corresponding normal mucosa, derived from 24 Dutch patients, was investigated for the loss of a marker mapping close to the region of p53 on chromosome 17p and for mutations in exons 5, 6, 7 and 8 of the p53 gene. The observed loss of heterozygosity of the marker on chromosome 17p was 36% of the informative cases, while 58% of the tumors contained a mutation in p53. This might be an indication that the mutation in p53 precedes the loss involving p53 on the homologous chromosome. Four tumors showed the presence of two different missense mutations in the p53 gene; in one of them the mutations involved the first two nucleotides of one and the same codon, while in a second case they were found within the same exon. In the remaining two cases the assessment of their situation, cis or trans, was not feasible. Six of the 18 mutations observed during this study were base transversions, including 3 G- > T substitutions. The hotspot codons 248, 273 and 282, were found to be involved in a third of the mutations.
对来自24名荷兰患者的一系列未经选择的结肠直肠腺癌及其相应的正常黏膜进行了研究，检测17号染色体短臂上靠近p53区域的一个标记的缺失情况，以及p53基因外显子5、6、7和8的突变情况。在信息充分的病例中，观察到17号染色体短臂上标记的杂合性缺失占36%，而58%的肿瘤存在p53突变。这可能表明p53突变先于同源染色体上涉及p53的缺失。4个肿瘤在p53基因中存在两种不同的错义突变；其中一个肿瘤的突变涉及同一个密码子的前两个核苷酸，而在另一个病例中，突变位于同一外显子内。在其余两个病例中，评估它们是顺式还是反式情况不可行。在本研究中观察到的18个突变中有6个是碱基颠换，包括3个G>T替换。热点密码子248、273和282参与了三分之一的突变。
