Centre National De La Recherche Scientifique

Université Paul Sabatier (toulouse Iii)

Institut Claudius Regaud

Cayla

Millegen

Institut National De La Sante Et De La Recherche Medicale

Christophe Cazaux

Jean-Sébastien Hoffmann

Daniel Drocourt

Gerard Tiraby

Jean-Christophe Bourdon

Michèle Tiraby

G&eacute;rard Tiraby

Thierry Louat

Laurence Servant

Khalil Bouayadi

Alice Machado Da Silva

Hakim Kharrat

Henri Roche

Jean-S&eacute;bastien Hoffmann

Pascal Fons

Jean Sébastien Hoffmann

Jean-Paul Reynes

Anne Vidal-Fernandez

The present invention relates to a method for diagnosing aggressiveness of a lung cancer in a patient from a lung cancer sample of the patient, comprising: a) detecting in vitro an expression profile of the DNA replication stress signature, the signature comprising the CDC6, CLASPIN, PLK1, and POLQ genes, as well as, optionally, RAD51; b) comparing the the expression profile to a reference expression profile, and d) diagnosing cancer aggressiveness from the comparison. Dedicated microarrays and kits are also described, as well as a method of selecting or adapting a suitable treatment.

Signature for the diagnosis of lung cancer aggressiveness and genetic instability

The present invention relates to a method for diagnosing aggressiveness and/or genetic instability of a cancer in a patient from a cancer sample of the patient. The method includes measuring in vitro the expression level of the POLQ gene and the expression level of a control gene in the patient cancer sample, calculating an expression level ratio of the expression level of POLQ to the expression of the control gene in the patient cancer sample, comparing the expression level ratio to a corresponding threshold value, and diagnosing cancer aggressiveness and genetic instability if the POLQ expression level ratio is superior to a corresponding threshold value. Dedicated microarrays and kits are also described, as well as a method of selecting a suitable treatment.

Signature for the diagnosis of cancer aggressiveness and genetic instability

The invention concerns a method for random mutagenesis comprising the replication of a DNA sequence in the presence of an efficient amount of at least a mutase, for example a Pol &#x3b2;, the random mutagenesis rate being at least of the order of 1 mutation for 400 base pairs. The replication product, optionally recombined and amplified, is cloned in an expression vector so as to generate mutated polypeptides which will be selected on the basis of the desired property or properties.

Use of mutagenic DNA polymerase for producing random mutations

The invention concerns the use of a vector expressing DNA polymerase &bgr; for the treatment of cancer or viral diseases such as AIDS.

Use of a vector expressing DNA polymerase &bgr; as medicine

The present invention relates to two groups of suicide hybrid genes in which genes from one group specifically activate the pyrimidine nucleobase analog 5-fluorocytosine and genes from the other group activate the pyrimidine nucleoside analog azidothymidine to derivatives toxic for mammalian cells.The present invention further relates to methods for the selective killing of transfected tumor cells or immune cells using a single suicide hybrid gene or the combination of two suicide hybrid genes selected for a complementarity in their antimetabolic action. The present invention also relates to eukaryotic vectors comprising two expression suicide gene units, the first permitting the sensitization of tumor cells to 5-fluorocytosine and the second permitting the sensitization of HIV-infected cells to Azidothymidine in a synergistic fashion.

Suicide genes and new associations of pyrimidine nucleobase and

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Plaisance du Touch, France

Christophe Cazaux