The aim of our group
is to individualize cancer risk assessment by evaluating the mutational
load and Distribution Assessment, MLDA, in biological fluids. This
technique is bases in the estimation of the prevalence of distinct
cell population within a tissue or a tumor using a quantitative mutation
detection technique of selected ras and p53 mutations. Serial analyses
of the mutational load helps in the identification of tumors in the
earliest stages. To do this we use an array-based assay that simultaneously
quantitates 23 selected loci (8 substitutions at codon 12 and 13
of the K-ras gene and 15 hotspots at exons 5 and 7 of the p53 gene.
This measure allows us calculation of the percentage of mutant alleles,
its sum is the total mutationa load.
In studies of pancreatic juice and fecal material we have shown that
this specificity has a high sensitivity and specificity in the non
invasive detection of colorectal and pancreatic tumors. Our preliminary
results suggest that it could be useful for the early diagnosis of
other tumors. We are currently completing studies assessing the diagnostic
usefulness of this measure and putting the emphasis in the assessment
of hereditary colorectal cancer family members. These clinical studies
are complemented with the analysis of heterogeneity in early lesions
such as aberrant crypt foci and adenomas and also in advanced metastatic
disease. We also evaluate the mutationa load in inflammatory bowel
disease, associated with an increased risk of developing carcinoma.
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