Topic
Mutant
About: Mutant is a research topic. Over the lifetime, 74520 publications have been published within this topic receiving 3477079 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: Analysis indicated that embryonic erythropoiesis, which occurs in the yolk sac, was not impaired by the c-myb alteration, but adult-type erythropsy was greatly diminished in c-Myb mutants, which is compatible with a role for c- myb in maintaining the proliferative state of hematopoietic progenitor cells.
1,058 citations
TL;DR: Recent studies on mutant p53 regulation, gain-of-function mechanisms, transcriptional effects and prognostic association are reviewed, with a focus on the clinical implications of these findings.
Abstract: Ample data indicate that mutant p53 proteins not only lose their tumour suppressive functions, but also gain new abilities that promote tumorigenesis. Moreover, recent studies have modified our view of mutant p53 proteins, portraying them not as inert mutants, but rather as regulated proteins that influence the cancer cell transcriptome and phenotype. This influence is clinically manifested as association of TP53 mutations with poor prognosis and drug resistance in a growing array of malignancies. Here, we review recent studies on mutant p53 regulation, gain-of-function mechanisms, transcriptional effects and prognostic association, with a focus on the clinical implications of these findings.
1,049 citations
TL;DR: Mutation of the p53 gene is the most frequently identified genetic change in human lung cancer; these findings suggest that simple immunohistological methods can provide strong evidence of such mutation.
1,048 citations
TL;DR: It is reported here that young heterozygous mice do not appear abnormal and do not develop retinoblastoma at a detectable frequency, however, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development.
Abstract: Human retinoblastomas can occur both as hereditary and as sporadic cases. Knudson's proposal that they result from two mutational events, of which one is present in the germ line in hereditary cases, has been confirmed by more recent molecular analysis, which has shown both events to involve loss or mutational inactivation of the same gene, RB-1 (ref. 2). RB-1 heterozygosity also predisposes to osteosarcoma, and RB-1 allele losses are seen in sporadic lung, breast, prostate and bladder carcinomas. RB-1 is expressed in most, if not all, tissues and codes for a nuclear phosphoprotein which becomes hypophosphorylated in the G0 growth arrest state and in the G1 phase of the cell cycle. To gain a further insight into the role of RB-1 we and other groups have generated mice carrying an inactivated allele of the homologous gene, Rb-1 (ref. 10), by gene targeting. We report here that young heterozygous mice do not appear abnormal and do not develop retinoblastoma at a detectable frequency. However, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development. Broadly similar results are reported by the other groups.
1,046 citations
TL;DR: Results demonstrate that PARP is a survival factor playing an essential and positive role during DNA damage recovery, and inactivated both alleles by gene targeting in mice.
Abstract: Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+: poly(adenosine-diphosphate-d-ribosyl)-acceptor ADP-d-ribosyltransferase, EC 2.4.2.30] is a zinc-finger DNA-binding protein that detects specifically DNA strand breaks generated by genotoxic agents. To determine its biological function, we have inactivated both alleles by gene targeting in mice. Treatment of PARP−/− mice either by the alkylating agent N-methyl-N-nitrosourea (MNU) or by γ-irradiation revealed an extreme sensitivity and a high genomic instability to both agents. Following whole body γ-irradiation (8 Gy) mutant mice died rapidly from acute radiation toxicity to the small intestine. Mice-derived PARP−/− cells displayed a high sensitivity to MNU exposure: a G2/M arrest in mouse embryonic fibroblasts and a rapid apoptotic response and a p53 accumulation were observed in splenocytes. Altogether these results demonstrate that PARP is a survival factor playing an essential and positive role during DNA damage recovery.
1,045 citations