Chromosome translocations in the common epithelial cancers are abundant, yet little is known about them. They have been thought to be almost all unbalanced and therefore dismissed as mostly mediating tumour suppressor loss. We present a comprehensive analysis by array painting of the chromosome translocations of breast cancer cell lines HCC1806, HCC1187 and ZR-75-30. In array painting, chromosomes are isolated by flow cytometry, amplified and hybridized to DNA microarrays. A total of 200 breakpoints were identified and all were mapped to 1 Mb resolution on bacterial artificial chromosome (BAC) arrays, then 40 selected breakpoints, including all balanced breakpoints, were further mapped on tiling-path BAC arrays or to around 2 kb resolution using oligonucleotide arrays. Many more of the translocations were balanced at 1 Mb resolution than expected, either reciprocal (eight in total) or balanced for at least one participating chromosome (19 paired breakpoints). Second, many of the breakpoints were at genes that are plausible targets of oncogenic translocation, including balanced breaks at CTCF, EP300/p300 and FOXP4. Two gene fusions were demonstrated, TAX1BP1-AHCY and RIF1-PKD1L1. Our results support the idea that chromosome rearrangements may play an important role in common epithelial cancers such as breast cancer.
Bladder cancer is the 6 th most common cancer worldwide and contributes significant excess mortality and morbidity. It often presents at a late stage when it is incurable, and the prognosis is poor.The local symptoms of bladder cancer-including haematuria, dysuria, frequency, nocturia and pain, have significant effects on quality of life and may require frequent inpatient admissions. As a palliative treatment, radiotherapy can be uniquely useful in providing targeted long term symptomatic control, although this must be balanced against the potential of causing toxicity. A variety of radiotherapy protocols have been developed for managing these symptoms. The results of several studies show that radiotherapy delivered in a hypofractionated regime (21 Gy in 3 fractions) can provide relief of these symptoms within a few weeks.Other commonly used regimes include 35 Gy in 10 fractions, 30 Gy in 5 fractions, a once weekly 36 Gy in 6 fractions, and a single 8 Gy fraction. In the palliative setting symptom resolution lasts for the majority of the patients remaining lifespan. Benefit is particularly clear for symptomatic haematuria and in these patients even single doses may provide rapid benefit. To maximise benefit from radiotherapy, studies are urgently needed to better estimate the prognosis of patients presenting with bladder cancer.
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