Chromosomal fragile sites studies were performed in 40 patients with lymphoma and 30 individuals as healthy controls. The results showed that there was a statistical difference of chromosomal aberration between the tw...Chromosomal fragile sites studies were performed in 40 patients with lymphoma and 30 individuals as healthy controls. The results showed that there was a statistical difference of chromosomal aberration between the two groups; The patients carried 46 fragile sites totally; 21 out of 46 fragile sites in lymphoma corresponded with cancer breakpoints, and 9 fragile sites were located in the bands where oncogenes exist. These suggest a certain association between fragile sites, cancer breakpoints and oncogenes and thus indicate a possible important role of fragile sites in the pathogenesis of lymphoma.展开更多
Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database...Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources). We mapped fragile sites to chromosomal bands and divided the 23 chromosomes into fragile and non-fragile sites. The frequency of rearrangements at the chromosomal location of clones found to be deleted or duplicated in the array/CGH analysis, provided by DECIPHER, was compared in Chromosomal Fragile Sites vs. non-Fragile Sites of the human genome. The POSSUM Web was used to complement this study. The results indicated 1) a predominance of rearrangements in CFSs, 2) the absence of statistically significant difference between the frequency of rearrangements in common CFSs vs. rare CFSs, 3) a predominance of deletions over duplications in CFSs. These results on constitutional chromosomal rearrangements are evocative of the findings previously reported by others relatively to cancer supporting the current line of evidence and suggesting that a common mechanism can underlie the generation of constitutional and somatic rearrangements. The combination of insights obtained from our results and their interrelationships can indicate strategies by which the mechanisms can be targeted with preventive medical interventions.展开更多
Background WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of th...Background WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present. Methods Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma. Results Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA （WWOX rate ratio=2.95, 95% CI 1.24-7.08; FHIT rate ratio=4.58, 95% CI 1.82-11.81） and Western blotting detectable protein （WWOX rate ratio=4.12, 95% CI 1.63-10.73; FHIT rate ratio=3.76, 95% CI 1.44-10.06）. For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance （P 〉0.05 for each analysis）. Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance （P 〉0.05 for each analysis）. Conclusion Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.展开更多
文摘Chromosomal fragile sites studies were performed in 40 patients with lymphoma and 30 individuals as healthy controls. The results showed that there was a statistical difference of chromosomal aberration between the two groups; The patients carried 46 fragile sites totally; 21 out of 46 fragile sites in lymphoma corresponded with cancer breakpoints, and 9 fragile sites were located in the bands where oncogenes exist. These suggest a certain association between fragile sites, cancer breakpoints and oncogenes and thus indicate a possible important role of fragile sites in the pathogenesis of lymphoma.
基金partially supported by CIGMH/FCM/UNL,under the project PEST-OE/SAU/UI0009/2011CMA/FCT/UNL,under the project PEst-OE/MAT/UI0297/2011.
文摘Chromosomal fragile sites (CFSs) are loci or regions susceptible to spontaneous or induced occurrence of gaps, breaks and rearrangements. In this work, we studied the data of 4535 patients stored at DECIPHER (Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources). We mapped fragile sites to chromosomal bands and divided the 23 chromosomes into fragile and non-fragile sites. The frequency of rearrangements at the chromosomal location of clones found to be deleted or duplicated in the array/CGH analysis, provided by DECIPHER, was compared in Chromosomal Fragile Sites vs. non-Fragile Sites of the human genome. The POSSUM Web was used to complement this study. The results indicated 1) a predominance of rearrangements in CFSs, 2) the absence of statistically significant difference between the frequency of rearrangements in common CFSs vs. rare CFSs, 3) a predominance of deletions over duplications in CFSs. These results on constitutional chromosomal rearrangements are evocative of the findings previously reported by others relatively to cancer supporting the current line of evidence and suggesting that a common mechanism can underlie the generation of constitutional and somatic rearrangements. The combination of insights obtained from our results and their interrelationships can indicate strategies by which the mechanisms can be targeted with preventive medical interventions.
文摘Background WWOX and FHIT are two candidate tumor suppressor genes located in active fragile sites, the damage of which has been associated with the development of breast cancer. The association of the expression of these genes and the development of breast cancer has not been fully explored. We evaluated mRNA and protein expression of WWOX and FHIT in breast tissue with normal histological appearances, atypical ductal hyperplasia, ductal carcinoma in situ, and invasive cancer to see if a progressive decline in expression was present. Methods Reverse transcription-polymerase chain reaction and Western blotting were used to evaluate the specimens for mRNA and protein expression, including 28 specimens with normal tissue, 28 specimens with atypical ductal hyperplasia, 33 specimens with ductal carcinoma in situ, and 51 specimens with invasive ductal carcinoma. Results Compared with in situ and invasive cancer specimens, both normal and atypical hyperplasia specimens had greater rates of detectable mRNA （WWOX rate ratio=2.95, 95% CI 1.24-7.08; FHIT rate ratio=4.58, 95% CI 1.82-11.81） and Western blotting detectable protein （WWOX rate ratio=4.12, 95% CI 1.63-10.73; FHIT rate ratio=3.76, 95% CI 1.44-10.06）. For both proteins, differences between normal and atypical hyperplasia specimens and between in situ and invasive carcinoma specimens were explainable by chance （P 〉0.05 for each analysis）. Within each histological category, differences among fractions of specimens showed that FHIT and WWOX mRNA and protein expression were explainable by chance （P 〉0.05 for each analysis）. Conclusion Expression of FHIT and WWOX decreases along with breast tissue progress from a normal histological appearance to atypical ductal hyperplasia, in situ cancer, and the final invasive cancer.
