Molecular diagnostics of solid malignant tumours.

Abstract

Three groups of genes have been identified which play a major role in determining the origin and spread of cancer: Oncogenes support the growth of tumour cells in a manner which does not depend on the tissue environment. They occur as proto-oncogenes in the genome of every cell in the body. If only one allele is excessively or inappropriately activated by mutation, they can change the phenotype of the cell lastingly and initiate malignant growth. Tumour suppressor genes hamper the growth of cells with DNA mutations. Both alleles must be mutated in the genome in order to block production of functional protein and to allow mutations to be passed on in their DNA to daughter cells. With an existing predisposition to cancer, one of the alleles is already mutated. The malignoma develops after a mutation occurs in the second allele. Mutator genes are responsible for maintaining the integrity of the genome and reliably transmitting the genetic code. A functional loss of both alleles increases error rates during DNA-replication. This can lead to mutations in oncogenes or tumour suppressor genes, and contribute to the origin or spreading of a malignoma. Tumour-modifier genes might turn out to be the genetic factors underlying the origin or even prevention of malignomas caused mainly by environmental factors. From experiments on mice it is known that these genes may be responsible for the incomplete penetrance of hereditary tumours. Demonstration of these genes using molecular diagnostic procedures will promote opportunities and knowledge in the field of oncology.