Presentation of activities

Diagnosis and monitoring:

The cancer biology unit is the site of the regional (Poitou-Charentes) platform for the molecular genetics of cancer; it has been awarded the labels of the French health care directorate general (DGOS) and the French national cancer institute (Inca). Clear evidence of the current importance of personalized medicine led lInstitut national du cancer to the realization, in 2006, that existing platforms needed to establish as a priority the development, in all regional cancerology centers, of an “identity card” for different tumors. Large-scale objectives, they have been formulated as follows:

Mesure 21: As a general rule, to guarantee equal access to treatments and innovations.

Action 21.2: More specifically, to develop platforms for the molecular genetics of cancer with access to molecular tests.

Labelled in 2006, our platform covers a population base, according to the 2008 census, of  1,745,123 inhabitants.

Personalized medicine is the possibility, for a given patient, to obtain his or her molecular profile: search for the mutations, translocations, fusion transcripts of his or her tumor, the objectives being identification of the anomaly/ies responsible for the activation of a signaling pathway essential to survival of the tumor and subsequent proposal, with regard to the anomaly, of targeted therapy. The therapeutic choice will consequently be based on identification of the anomaly or bio-marker.

The laboratory consists in two medical units (MU):

Medical molecular oncology unit  (Pr L. Karayan-Tapon).

Medical molecular hematology unit (Dr J.-C. Chomel).

The two MUs provide diagnosis and molecular monitoring of the solid tumors and malignant hemopathies treated at the Poitiers CHU and in the Poitou-Charentes region. The final goals, whatever the type of cancer, are 1) to stratify patients as soon as they are diagnosed so that the most suitable treatment can be offered, 2) to monitor treatment effectiveness at the molecular level and 3) to predict as early as possible a relapse.

Predictive markers determining access to a targeted therapy: EGFR mutations, RAS (KRAS, NAS) mutations, BRAF mutations, KIT/PDGFRa mutations, PI3K mutations, HER2 mutations, HER2 amplification, ALK translocations,  ROS1 translocations, detection of rearrangements BCR-ABL, PML-RARa, FIP1L1-PDGFRa,  BCR-ABL mutations, JAK2 mutation, CALR insertions/deletion.

Markers orienting the diagnostic process: Microsatellite instability,  MLH1 promoter methylation, heterozygosity 1p/19q loss, mutations IDH1/2 mutations, detection of  CBFB-MYH11, AML1-ETO,TEL-AML1, E2A-PBX, SIL-TAL, MLL, IgH-Bcl1 and IgH-Bcl2 rearrangements, highlighted tandem repeat of  FLT3,NPM1 mutations, expression of  cyclin D1

Monitoring markers: MGMT methylation,  quantification of mutated ARNm BCR-ABL, PML-RARa, CBFB-MYH11, AML1-ETO, WT1, NPM1; TEL-AML1, E2A-PBX, SIL-TAL; alleles JAK2 V617F, MLL

Activity: around 40,000 actions, 4.2M  B/BHN a year.

Technologies / methods applied in the laboratory

The following technologies have been developed in the laboratory:

  • Extraction of nucleic acids (genomic DNA and total RNA) from different biological samples (blood, bone marrow,  ganglions, tumor, pleural liquids), paraffin sections and frozen tissue.
  • Control and dosing of nucleic acids.
  • Reverse transcription.
  • Search for molecular rearrangements (fusion transcripts) by RT-PCR at end point and in real time
  • Search for known point mutations by allele-specific PCR RFLP, PCR , allele-specific PCR in real time.
  • Search for mutations by DGGE.
  • Characterization of mutations by pyrosequencing
  • Characterization of mutations by direct double-stranded sequencing.
  • Mutant allele assay by quantitative PCR in the presence of a standard range of plasmids.
  • Fusion transcript assay by quantitative RT-PCR in presence of a standard range of plasmids (evaluation of residual disease).
  • FISH on paraffin-embedded tissue for cytogenetics of solid tumors.
  • High-throughput sequencing  (miSeq/Illumina).

Pedagogical project

One of the major present-day priorities in cancerology is improved knowledge of applied cancer biology. Indeed, organization of personalized medicine in cancerology necessitates not only “true” general knowledge of the routes of carcinogeneis, but also specific knowledge of the cancer biology of a given organ with the highlighting of driver genes and the functional disruptions arising from the ensuing oncogene addiction. Treatment of cancer patients is multidisciplinary, and the  cancer biology teaching necessitates a multidisciplinary approach.

It is important, given today’s evolution in cancer biology, to train professionals with competence in the biology of cancer, specifically as regards biological validation of health-oriented somatic gene examinations.  Validation analyses are presently carried out on resection specimens for solid tumors, and also in blood, bone marrow and lymph nodes for malignant hemopathies. In the coming years these diagnostic, prognostic and theranostic tests will evolve and will probably involve biological liquids: circulating DNA/RNA, circulating cancer cells…

 

Participation in the activities of cooperating groups:  Cancéropôle GO, INCa, ANOCEF

Supervising university unit:  Cancerology –Radiotherapy 4702

chumag63_traitement-cancerTowards targeted cancer treatment
CHU Magazine n°63 – December 2011

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