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RER Phenotype (rer + phenotype)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Analysis of the human APC mutation spectrum in a saccharomyces cerevisiae strain with a mismatch repair defect

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2003
Kazunori Otsuka
Abstract Somatic APC mutations in colorectal tumors with an RER phenotype reflect excessive frameshift mutations, especially in simple repetition tracts within the coding sequence. Because this type of mutation is characteristic of cells with a deficient DNA MMR system, the APC mutation signature of RER tumors may be attributable to a defect in the MMR system. However, there is little experimental evidence to prove that the spectrum of mutations and the APC gene distribution are directly influenced by MMR system defects. We therefore examined the mutation spectrum of the MCR of the APC gene after transfection into both MMR-proficient and MMR-deficient yeast strains and compared it with a previously reported human APC mutation database. Small insertions or deletions in mono- or dinucleotide repeats were more common in the MMR-deficient than in the MMR-proficient strain (91.2% vs. 38.1%, Fisher's exact test p < 0.0001). Furthermore, the 2 mutation hot spots, 4385,4394(AG)5 and 4661,4666(A)6, found in the yeast system corresponded with those in human tumors. Combining our data with those from human tumors, there appears to be hypermutable mutations in specific simple repetitive sequences within the MCR, which are more prevalent in MMR-deficient cells and RER tumors than in MMR-proficient cells and non-RER tumors. We therefore consider that the differences in the spectra of RER and non-RER tumors are attributable at least in part to the MMR system of the host cells. © 2002 Wiley-Liss, Inc. [source]

Axonal secretion of reelin by cajal-retzius cells: Evidence from comparison of normal and RelnOrl mutant mice

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2001
Paul Derer
Abstract A novel secretory pathway has been identified in the study of mice homozygous for the RelnOrl mutation, a line characterised by the defective secretion of the large extracellular matrix glycoprotein Reelin. By using both light and electron microscopy, immunohistochemical studies for Reelin in these mutants identified morphological changes in their Cajal-Retzius cells (CR cells). The CR cells of the mutant displayed the characteristic features of bipolar, tangentially elongated neurons with a dendritic proximal pole and an axonal cone at the opposite end of the soma. At either pole, cisterns of prominent rough endoplasmic reticulum (RER) were found to be rich in Reelin. However, the Reelin-positive RER cisterns of the axonal cones were hugely dilated in homozygous RelnOrl mice as compared with their wild type counterparts. CR cell axons displayed beads throughout their length, each contained a smooth spheroidal cistern filled with Reelin-immunoreactive fibrillar material, and were increased in number and size in RelnOrl mice. RER phenotype was rescued in the RelnAlb2 mice, a mutation in which no Reelin protein is produced. We propose that the RER dilations viewed in the RelnOrl mutation are due to the accumulation of the defective Reelin protein, and the large axonal beads in RelnOrl mice reflect the accumulation of truncated Reelin as the result of defects in its secretion. These observations point to an original, hitherto unrecognised, mechanism of secretion by bulk transport in smooth cisterns from the axonal cone into the axon, followed by secretion in the cortical marginal zone from the axonal cisterns that we have named axonal reelin reservoirs. J. Comp. Neurol. 440:136,143, 2001. © 2001 Wiley-Liss, Inc. [source]

The replication error phenotype is associated with the development of distant metastases in hormonally treated patients with breast carcinoma

CANCER, Issue 5 2004
Anees Chagpar M.D., M.Sc.
Abstract BACKGROUND The positive replication error (RER+) phenotype defines a distinct subgroup of tumors with specific clinical, pathologic, and molecular features that have been documented well in hereditary nonpolyposis colon carcinoma (HNPCC). More recently, this phenotype also has been described in breast carcinoma. METHODS To determine the effect of RER phenotype on prognosis in patients with breast carcinoma, the authors examined matched archival tumor and normal tissue from 100 women with Stage I and Stage II breast carcinoma, all of whom were treated with hormonal therapy. Patients had been followed for a minimum of 5 years or until death. Seven microsatellite loci were examined, including hMLH1 (3p22, D3S1611), hMSH2 (2p16, D2S123), NM23-H1 (17q21), TP53-Dint (17p13), TP53-Penta (17p13), APC (5q21, D5S346), and HPC1 (1q24, D1S2883). The RER+ phenotype was defined as the presence of allelic shifts at three of the seven loci examined. RESULTS Twenty-five percent of patients were classified with the RER+ phenotype based on these criteria. The two groups, women with positive RER status and women with negative RER status, were comparable in terms of other factors that may influence prognosis: age, tumor size, lymph node status, disease stage, and estrogen receptor status. The development of distant metastases to the lung, liver, or brain was correlated significantly with the positive RER phenotype, with a relative risk of 2.625 (95% confidence interval, 1.059,6.057). CONCLUSIONS The presence of high-frequency RER+ may predict for the development of distant metastatic disease in patients with early-stage breast carcinoma whoa re treated with hormonal therapy. Cancer 2004;100:913,9. © 2004 American Cancer Society. [source]