RESUMO
Here we review a panel of oncogene products, proteases and markers of proliferation that have shown potential as prognostic indicators in primary breast cancer. The relative merits of specific genetic mutations as well as alterations at the protein level are discussed. Finally an assessment is made of the transfer of knowledge from the laboratory to the bed-side.
Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Predisposição Genética para Doença , Humanos , Indicadores e Reagentes , Mutação/genética , Proteínas de Neoplasias/genética , Prognóstico , Saúde da MulherRESUMO
Telomerase, the enzyme responsible for maintenance of the telomeres, is absent from the vast majority of somatic cells but is present in most tumours. Little is known about how telomerase is activated in cancer, although it is thought vital for immortalisation to occur. The aim of our study was to identify genetic changes associated with telomerase activity. Thirty-three breast carcinomas were assessed for telomerase activity using the PCR based TRAP assay, and genetic changes by comparative genomic hybridisation (CGH). Seventy-five percent of the tumours were telomerase positive, and these were further divided into low or high level telomerase activity groups. A large number of genetic aberrations were identified but 4 chromosomal regions were identified that correlated with the telomerase status of the tumour. Gain of 1q correlated with telomerase negative tumours, gain of 3q correlated with high level telomerase activity. Gain of 8q correlated with telomerase positive tumours and furthermore with high level telomerase activity; deletion of 17p also correlated with high level telomerase activity. CGH analysis of breast tumours in conjunction with telomerase status has supported early results suggesting the involvement of the telomerase hTR, c-myc and p53 genes in the control of telomerase activity. These genes are located on chromosomes 3q, 8q and 17p. Most importantly, our results have identified the involvement of gene(s) located on chromosome 1q in telomerase expression.
Assuntos
Neoplasias da Mama/genética , Aberrações Cromossômicas , Telomerase/metabolismo , Neoplasias da Mama/enzimologia , Cromossomos Humanos Par 8 , Feminino , Genes myc , Genes p53 , HumanosRESUMO
Breast cancer is characterised by a number of genetic aberrations. Our purpose was to use comparative genomic hybridisation (CGH) to screen breast carcinomas for copy number changes: 44 ductal and 8 lobular carcinomas were studied and a large number of genetic aberrations identified. Many of these showed similarity to previous CGH results, however, a number of loci not previously shown to have undergone frequent change were identified. This included copy number gains affecting chromosomes 1p, 4q, 5q, 6q and 13q. Furthermore, we have identified 2 regions of copy number change, the gain on 5p and deletion of 16q, which correlated with lobular carcinomas. Our results highlight several areas of the genome that may be important in the molecular genetics of breast cancer.