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Methods of molecular analysis: mutation detection in solid tumours Frayling IMMol Pathol 2002[Apr]; 55 (2): 73-9Most mutation detection techniques are unsuitable for routine use on solid tumours. Important parameters include sensitivity, specificity, efficiency, use of existing resources, and cost. In the UK, < 0.2% of service genetics laboratory activity involves mutation analysis in tumours (usually for family studies), mainly because it is time consuming/labour intensive (thus expensive) and DNA extracted from formalin fixed, paraffin wax embedded tissue is of low quality and yield. The small size of DNA fragments obtained from tissue blocks limits the polymerase chain reaction, the basis of most mutation detection methods. Other, biological, factors include: (1) heterogeneity of mutations within and between tumours, (2) variation in type and site of mutations in any one gene, (3) normal tissue harbouring mutations, (4) few genes are mutated in most of any one tumour type, and (5) few clinically useful correlations with genetic changes have been found. Present research is centred on correlating single gene mutations with various clinicopathological features, but the pattern of mutations in a combination of genes will probably prove more useful. Microsatellite instability, however, appears to be worth testing for in both familial and sporadic tumours, particularly of the colorectum.|*DNA Mutational Analysis[MESH]|*Microsatellite Repeats[MESH]|Base Pair Mismatch[MESH]|Colorectal Neoplasms/*diagnosis/*genetics[MESH]|Electrophoresis[MESH]|Humans[MESH]|Polymerase Chain Reaction/methods[MESH]|Polymorphism, Single-Stranded Conformational[MESH]|Sensitivity and Specificity[MESH] |
