Application of molecular genetics and cytogenetics to breast cancer and soft tissue sarcomas.
Over the last decade there have been considerable advances in understanding of the molecular events involved in the initiation and progression of a wide range of solid tumours. In many instances, cytogenetic abnormalities have been the first indication that there is a mutated gene at a particular locus. In colonic polyposis, for example, the loss of 5q material in a man with the disease indicated the importance of the region and led to the subsequent cloning of the gene. Interestingly, loss of this tumour suppressor gene is also seen in approximately 20%-50% of sporadic colorectal carcinomas, which suggests that it may be important to study these inherited syndromes to identify genes that may be more widely involved in carcinogenesis. It is also important to realize that the order in which different molecular events occur is unlikely to fit into predictable chronological patterns, and that there will be great variation in the molecular defects of tumours that otherwise appear morphologically similar and have a common pattern of clinical presentation and progression. This is because established tumours are probably composed of a number of subclones at the molecular level, and clonal selection will only take place if a particular mutation provides a selective growth advantage or it is necessary for a stage in progression, such as invasion or metastasis. Multiple sites of loss of heterozygosity (LOH) have been identified in a range of tumours, many of which may be sites of as yet unidentified tumour suppressor genes.(ABSTRACT TRUNCATED AT 250 WORDS)
Gusterson
B
B
Section of Cell Biology and Experimental Pathology, Institute of Cancer Research, London, U.K.
Shipley
J
J
Crew
J
J
D001943:Breast Neoplasms / Q000235:genetics*; D002278:Carcinoma in Situ / Q000235:genetics; D018275:Carcinoma, Lobular / Q000235:genetics; D002869:Chromosome Aberrations; D005260:Female; D015321:Gene Rearrangement; D005799:Genes, Dominant; D016147:Genes, Tumor Suppressor; D006801:Humans; D008967:Molecular Biology; D012509:Sarcoma / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000235:genetics*