Biomedical subjects

Anne Gibaud

Publications and source records attributed to Anne Gibaud.

3 recordsLinked to original sources

PubMed2006

Specific TP53 mutation pattern in radiation-induced sarcomas.

The mutagenic properties of ionizing radiation are well known, but the presence of specific mutations in human radiation-induced tumours is not established. We have studied a series of 36 secondary sarcomas arising in the irradiation field of a primary tumour following radiotherapy. The allelic status and the presence of mutations of the TP53 gene were investigated. The mutation pattern was compared with data from sporadic sarcomas recorded in the IARC TP53 somatic mutations database. A high proportion (58%) of the radiation-induced sarcomas exhibited a somatic inactivating mutation for one allele of TP53, systematically associated with a loss of the other allele. The high frequency (52%) of short deletions observed in the mutation pattern of radiation-induced sarcomas may be related to the induction of DNA breaks by ionizing radiation. The lack of hyper-reactivity of CpG dinucleotides and the presence of recurrent sites of mutation at codons 135 and 237 seem also to be specific for radiation tumorigenesis.

Adult↗

PubMed2004

Quantitative fish determination of chromosome 3 arm imbalances in lung tumors by automated image cytometry.

BACKGROUND: Clonal heterogeneity is a major difficulty in the analysis of chromosome rearrangements within tumor tissue. Using in situ hybridization, a cell-to-cell analysis can be performed and should allow a better understanding of the genetic process. In addition, detection of pre-neoplastic lesions with only a few cells involved may improve the diagnosis of such lesions and their precocious treatment. MATERIAL/METHODS: Automated analysis was performed on tissue sections with our previously described two-color fluorescence in situ hybridization-based method for quantitative determination of chromosome arm imbalance. The imbalance between the long and short arms of chromosome 3 was determined in 24 cases of non-small-cell and small-cell lung cancers in which only small snap-frozen sections were used, allowing other simultaneous molecular analyses, such as TP53 gene mutation detection. RESULTS: Specifically developed software allowed localization of each nucleus within the section with regard to its chromosome imbalance and to reconstitute a multi-clonal panel within an apparently homogeneous sample. In some cases, discrepancies in the imbalance values were observed between the biopsy and the tumor obtained after surgery from the same patient. CONCLUSIONS: The discrepancies observed between biopsies and tumors, likely linked to the samples' heterogeneity, demonstrate the necessity to analyze tissue sections collected at various locations. The fully automated approach developed in this study rendered such investigations possible.

Cell Transformation, Neoplastic↗

PubMed2003

Rapid prenatal diagnosis of Down syndrome using quantitative fluorescence in situ hybridization on interphase nuclei.

OBJECTIVES: Presently, conventional cytogenetic analysis of metaphase chromosomes remains the reference approach in prenatal diagnosis. However, this method is labor-intensive and time-consuming. The first step toward the rapid identification of aneuploidies is achieved by interphase fluorescence in situ hybridization (FISH) with centromeric or locus-specific probes. Spot counting using this type of probes is a reliable approach, but is very time-consuming with some technical and biological limitations. In this study, we present a new FISH method using image cytometry for the detection of trisomy 21 within interphase nuclei. METHODS: The method is based on a comparative quantitation of the fluorescence signals emitted by whole chromosome 21 and 22 painting probes cohybridized on interphase nuclei. The chromosomal imbalance was determined with an automated image cytometer by detecting an abnormal ratio of both fluorescence emissions when compared with the ratio obtained in normal cells. RESULTS: Ten blood samples and twenty amniotic fluids were analyzed. Results from FISH and standard cytogenetics were compared and 100% correlation was achieved. CONCLUSIONS: This method, which enables an easy detection of chromosomal imbalances without a need for metaphase preparations, can be applied to the diagnosis of trisomy 21 and extended to other disorders with chromosomal imbalances. Compared to other interphase FISH techniques, it avoids spot-scoring difficulties.

Adult↗