Association of the germline TP53 R337H mutation with breast cancer in southern Brazil

<p>Abstract</p> <p>Background</p> <p>The germline <it>TP53</it>-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT) in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context.</p> <p>Methods</p> <p>We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing <it>TP</it>53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H.</p> <p>Results</p> <p>The R337H mutation was found in three patients but in none of the controls (p = 0.0442). Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant <it>TP53 </it>allele rather than the wild-type allele. Polymorphisms were identified within the <it>TP53 </it>(R72P and Ins16) and <it>MDM2 </it>(SNP309) genes that may further diminish <it>TP53 </it>tumor suppressor activity.</p> <p>Conclusion</p> <p>These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant <it>TP53 </it>alleles can differentially influence tumor susceptibility.</p

Expression of heme oxygenase-1 mRNA in vitreous-treated retinal pigment epithelial cells

Low passage donor retinal pigment epithelial (RPE) cells were incubated with or without vitreous for up to 24 h. RNA was extracted at each time point and heme oxygenase-1 (HO-1) mRNA was measured by qPCR. Ribosomal protein, large, P0 (RPLP0) was used as an internal standard to correct for small differences in the amount of cDNA used in each reaction. Each point at a particular time indicates a different RPE/vitreous donor pair. The number of donor/vitreous pairs examined at each time point is shown. At 6, 12, and 24 h, REST-XL analysis indicated that HO-1 mRNA was significantly increased (p<p><b>Copyright information:</b></p><p>Taken from "Vitreous induces heme oxygenase-1 expression mediated by transforming growth factor-β and reactive oxygen species generation in human retinal pigment epithelial cells"</p><p></p><p>Molecular Vision 2007;13():66-78.</p><p>Published online 24 Jan 2007</p><p>PMCID:PMC2503184.</p><p></p

Expression of metallothionein mRNAs in vitreous-treated retinal pigment epithelial cells

Retinal pigment epithelial (RPE) cells were incubated with or without vitreous for up to 48 h. RNA was extracted at each time point and RNAs for metallothionein-1a (MT-1a; quadrangle) and metallothionein-2a (MT-2a; diamond) were measured by qPCR. Ribosomal protein, large, P0 (RPLP0) was used as an internal standard to control for small differences in the amount of cDNA used in each reaction. Each point at a particular treatment time indicates a different RPE/vitreous donor pair. The number of donor/vitreous pairs examined at each time point is shown. At all time points, REST-XL analysis indicated that MT-1 and MT-2a mRNAs were significantly increased (p<p><b>Copyright information:</b></p><p>Taken from "Vitreous induces heme oxygenase-1 expression mediated by transforming growth factor-β and reactive oxygen species generation in human retinal pigment epithelial cells"</p><p></p><p>Molecular Vision 2007;13():66-78.</p><p>Published online 24 Jan 2007</p><p>PMCID:PMC2503184.</p><p></p