رسالة جامعية
From Chromosome to Gene by Mapping Chromosomal Abnormalities in Cancer in Order to Find Targeted Pharmaceutical Agents ; Du chromosome au gène par un criblage global des altérations génomiques dans la malignité pour isoler de nouvelles cibles thérapeutiques
| العنوان: | From Chromosome to Gene by Mapping Chromosomal Abnormalities in Cancer in Order to Find Targeted Pharmaceutical Agents ; Du chromosome au gène par un criblage global des altérations génomiques dans la malignité pour isoler de nouvelles cibles thérapeutiques |
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| المؤلفون: | Toujani, Saloua |
| المساهمون: | Génétique des tumeurs (U985), Institut Gustave Roussy (IGR)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Sud - Paris XI, Alain Bernheim |
| المصدر: | https://theses.hal.science/tel-01084902Test ; Génétique. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA11T027⟩. |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Chromosome, Gene, Cancer, Comparative genomic hybridization, Gène, Hybridation génomique comparative, [SDV.GEN]Life Sciences [q-bio]/Genetics |
| الوصف: | Much of our current understanding of cancer is based on the hypothesis that it is a genetic disease, arising as a clone of cells that expand in an unregulated fashion because of somatically acquired mutations. High-throughput tools for nucleic acid characterization, such as array comparative genomic hybridization (aCGH), now provide the means to conduct comprehensive analyses of somatic anomalies in the oncogenome.In the first part of our work we have carried out a fine mapping of additional chromosomal anomalies in Burkitt lymphoma (BL). The hallmark of this disease is the translocation t(MYC;IG). We have applied whole-genome 244K and 44k oligonucléotides aCGH to 15 cells lines and 12 primary tumors of BL respectively. Karyotype and FISH analysis were used to validate aCGH results. As expected, all translocations remained undetectable with aCGH. More than half of the copy number alterations (CNAs) < 2 Mb were mapped to Mendelian CNVs, including GSTT1, and BIRC6. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs, gains were found in 1q, 13q, 7q, 8q, 2p, 11q and 15q. Losses were found in 3p, 4p, 4q, 9p, 13q, 6p, 17p, 6q,11pterp13 and 14q12q21.3. Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q: 1q21.1q25.2, 1q32.1 et 1q44. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2, BCL9 and PIAS3. Only BCL9 high level transcrit was noted on oligonucleotide microarray gene expression that was done on 15 cells lines. BCL9, was implicated in a LAL B translocation t(1;14)(q21;q32) and it is a member of MYC pathway. The 13q31.3q32.1, 89.58–96.81 Mb MCR contained an amplicon with several genes. The miR-17-92 cluster, upregulated on mirnome analysis that was done on 15 cells lines, is the gene driver of 13q MCR. The miR-17-92 cluster is a member of MYC pathway. The 9p21.3 MCR harbored p16INK4A/p15INK4B locus which ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | French |
| العلاقة: | NNT: 2012PA11T027; tel-01084902; https://theses.hal.science/tel-01084902Test; https://theses.hal.science/tel-01084902/documentTest; https://theses.hal.science/tel-01084902/file/VA_TOUJANI_SALOUA__-_05062012.pdfTest |
| الإتاحة: | https://theses.hal.science/tel-01084902Test https://theses.hal.science/tel-01084902/documentTest https://theses.hal.science/tel-01084902/file/VA_TOUJANI_SALOUA__-_05062012.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.C131CD69 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |