Cytogenetic, FISH, and molecular results of 20 cases with de novo tandem duplications of 18 diVerent autosomal chromosome segments are reported. There were 12 cases with direct duplications, three cases with inverted duplications, and five in whom determination of direction was not possible. In seven cases a rearrangement between non-sister chromatids (N-SCR) was found, whereas in the remaining 13 cases sister chromatids (SCR) were involved. Paternal and maternal origin (7:7) was found almost equally in cases with SCR (3:4) and N-SCR (4:3). In the cases with proven inversion, there was maternal and paternal origin in one case each. Twenty three out of 43 cytogenetically determined breakpoints correlated with common or rare fragile sites. In five cases, including all those with proven inverse orientation, all breakpoints corresponded to common or rare fragile sites. In at least two cases, one with an interstitial duplication (dup(19)(q11q13)) and one with a terminal duplication (dup(8) (p10p23)), concomitant deletions (del(8) (p23p23.3) and del(19)(q13q13)) were found. (J Med Genet 2000;37:281-286)

Signaling pathways activated by epidermal growth factor receptors (EGFRs) are important in lung carcinogenesis. New treatment strategies with EGFR-targeting drugs provided improvements in management of lung cancer. However, molecular mechanisms underlying resistance to these drugs need to be evaluated. Surgically resected samples were obtained from 50 patients with non-small-cell-lung cancer. PTEN, Mcl-1 and EGFR protein expression levels were evaluated by Western-blot. Direct sequencing was performed to investigate EGFR tyrosine kinase domain mutations. We detected c.2235-2249 (pGlu746-Ala750del) mutation in exon 19 in two patients with adenocarcinoma histology. Elevated expression levels of both Mcl-1 isoforms (Mcl-1S and Mcl-1XL) and EGFR proteins were found in 15 (30%) and 23 (46%) of the cases, respectively. Reduced PTEN protein expression levels were observed in 17 (34%) of the cases. PTEN expression level was reduced in 26% of cases that showed increased EGFR expression. Also, increased expression of Mcl-1 protein was observed in 26% of cases with EGFR overexpression. One of the cases harboring pGlu746-Ala750del mutation had increased levels of Mcl-1 and decreased PTEN expression levels. Our results indicate that, in addition to lack of PTEN expression, elevated levels of the Mcl-1 protein might be one of the important intrinsic mechanisms protecting non-small-cell-lung cancer cells from apoptosis induced by several compounds. Therefore, EGFR mutations in conjunction with evaluation of Mcl-1 and PTEN expression levels in large cohorts might provide important clues for improvements of new treatment strategies in non-small-cell-lung cancer management.

Attenuating amyloid-beta mediated neurodegeneration is of major therapeutic consideration in the potential treatment of Alzheimer disease. Previously, we found that a high dietary consumption of retinoic acid was associated with a reduced incidence of Alzheimer disease. Therefore, in this study, we investigated whether amyloid-beta mediated cell death in primary hippocampal neurons could be prevented by retinoic acid isomers. Our results suggest that retinoic acid isomers, including all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid, may play an important role in protecting neurons from amyloid-beta -induced cell death. Retinoic acid may therefore afford a novel therapeutic mechanism for the treatment and prevention of Alzheimer disease.

Survival motor neuron 1 (SMN1) gene analysis should be considered if clinical features are consistent with SMA, even if pathological or electrophysiological findings demonstrate peripheral sensorimotor polyneuropathies.

Introduction: The prognostic significance of PTEN protein loss in bladder cancer is not well established. The objective of this study was to investigate the PTEN expression profile in superficial noninvasive papillary transitional cell carcinoma (TCC) versus invasive TCC and compared the results with pathological and clinical parameters. Materials and Methods: Bladder tumor samples were obtained from 29 patients who underwent surgery for superficial (n = 11) and invasive (n = 18) bladder cancers at the Akdeniz University Hospital. The patient profile including sex, age, histological grade and the stage, presence of carcinoma in situ, cystoscopy findings (tumor size, location, multiplicity) were obtained by examining the patients’ medical records. No patient received anticancer agents prior to the operation. Western blotting was performed using bladder carcinoma samples in order to determine the level of PTEN protein expression for each patient. Results: Only 4 (13.7%) patients with bladder carcinoma manifested a decrease in the level of PTEN expression. Regarding the correlation between tumor stage and the PTEN expression, with the exception of patient 23 all patients who displayed a reduction in PTEN expression had muscle-invasive TCC. Conclusion: Future studies with a clinical follow-up will be needed to determine if those superficial tumors with decreased PTEN expression are going to progress to a later stage. Based on our results PTEN by itself does not seem to be a good candidate as an independent marker to predict the behavior of bladder cancers.