AIMS: Loss of heterozygosity (LOH) may vary almost randomly within a @entity14 due to the heterogeneous morphologic character of these @entity5 . Despite this, as a rule, single biopsies are the source of genetic material used in studies of markers important for prognosis, clinical behaviour of the disease, or susceptibility of specific @entity5 to different treatment modalities. METHODS: To evaluate the importance of intratumoural variation for the results of analysis of LOH and point mutations in @entity14 and to determine the frequency of genetic alterations in different types of pre- @entity5 areas of the @entity5 , 36 consecutively operated @entity1 with @entity14 were studied. After fixation, specimens were mounted on large slides containing the whole @entity5 . The specimens were sub classified into different areas defined as normal tissue, normal tissue closely adjacent the @entity5 mass, @entity652 , @entity1141 and @entity3 cells. These areas were dissected and subjected to DNA extraction. RESULTS: The extracted genomic DNA was studied for LOH at chromosome 5q, 17p, and 18q and for @entity984 mutations. Overall, a correlation between the intratumoural degree of @entity5 progression and the frequency of LOH and @entity984 mutations was seen. These correlations were significant (p<0.008) except for @entity1141 /adenomatous tissue versus @entity3 . @entity124 was found in 9% of the @entity5 , all except one in invasive parts of the @entity5 . CONCLUSIONS: This study demonstrates a statistical correlation between intratumoural differences in @entity5 degree of dedifferentiation and genetic instability in terms of LOH and point mutations of the @entity984 gene in @entity14 . The importance of a careful dissection in order to localise the region with the highest probability of genetic aberrations and multiple biopsing must not be neglected. The observation that the prevalence of @entity984 mutations and LOH are correlated to the degree of dedifferentiation within a @entity14 is in line with the concept that selected cell clones are responsible for the @entity5 .

Distribution of genetic variants in preneoplastic areas of XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity124 :: ('MESH:D053842', 'Disease') :: ['Microsatellite instability'] @entity5 :: ('MESH:D009369', 'Disease') :: ['neoplastic progression of the tumour', 'neoplastic', 'tumours', 'tumour'] @entity984 :: ('3845', 'Gene') :: ['k-ras'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal tumour', 'colorectal carcinoma', 'colorectal cancer'] @entity3 :: ('MESH:D009362', 'Disease') :: ['invasive cancer'] @entity652 :: ('MESH:D000236', 'Disease') :: ['adenoma'] @entity1141 :: ('MESH:C535662', 'Disease') :: ['dysplasia']
@entity14 :: (MESH:D015179,Disease) :: ['colorectal tumours']
