Allelotyping identification of genomic alterations in rectal chromosomally unstable tumors without preoperative treatment

Abstract Background Numerous studies reported genomic alterations in colorectal human tumors but few focused on rectal tumors with the specification of preoperative-treated or untreated tumors. The goals of this study were to list chromosome allelic imbalances and correlate their frequency with tumor progression and to identify potential molecular markers of progression in rectal chromosomally unstable tumors without preoperative treatment. Methods Genomic alterations of 57 rectal tumors assessed by allelotyping targeting 33 chromosomal loci, were clusterised and compared to those of 151 left colon tumors. Results Clustering separated the rectal tumors without preoperative treatment into three subtypes according to the allelic imbalance frequency and genomic alteration associations. The tumors without preoperative treatment displayed a significantly higher allelic imbalance frequency (54%) than the tumors with preoperative treatment (33%), suggesting that treatment could target highly altered tumor clones. Interestingly, the survival analysis identified three potential prognostic molecular survival markers, D1S197, D5S430, and D14S65, for tumors without preoperative treatment. Conclusion Based on the genomic status of 33 chromosomal loci, we observed that rectal tumors without preoperative treatment segregate according to the global allelic imbalance frequency but without correlation to the tumor progression. Moreover, the detailed associations of alterations in rectal tumors are different from those described in colon tumors suggesting that rectal and left tumors should be considered as separate entities. Finally, potential prognostic genomic molecular markers for survival are proposed which status could specify the clinical course of the tumors.</p

Evidence for various 20q status using allelotyping, CGH arrays, and quantitative PCR in distal CIN colon cancers.

International audienceThe genomic aberration profile of chromosome 20q in distal CIN colon carcinomas was analysed using allelotyping and CGH arrays. Allelotyping revealed carcinomas with allelic imbalance along the full long arm, and carcinomas with fully non-aberrant 20q. Oligonucleotide-based CGH showed that among the carcinomas without allelic imbalance, 47% had in fact a gain. In this subgroup, quantitative PCR for the TOPI gene (20q12) confirmed this gain, and fluorescence in situ hybridization showed that the chromosome 20q gain resulted from tetra/polysomy instead of aneusomy. The 20q gain correlated with a high frequency of aberrations, with allelic imbalance at TP53 locus but not at APC locus, and carcinomas with a disomic 20q showed low frequency of genomic aberrations and were significantly associated to mucinous phenotype. The prognostic value of 20q amplification was not demonstrated in this study. These results indicate that on the basis of aberration frequency, chromosome 20q and TP53/APC locus status, distal CIN carcinomas harbor a high degree of genetic heterogeneity suggesting several pathways for carcinogenesis. This study also indicates that allelotyping needs to be carried out with a complementary technique, such as quantitative PCR

RNA Aptamers Targeting Integrin α5β1 as Probes for Cyto- and Histofluorescence in Glioblastoma

International audienc

341

Recherche ● La théorie de la gouvernance élargie est appliquée à l’analyse de la décision d’investissement dans les exploitations laitières. ● Le maintien ou le démantèlement des offices laitiers dans différents pays (Australie, Canada, Nouvelle-Zélande, Royaume-Uni) est analysé à partir de la théorie du changement de paradigme politique. ● Les allégations nutritionnelles (au sujet des formes allégées de produits laitiers) ont des effets positifs sur les ménages présentant un risque de santé. Mais les relations entre les produits (effets de substitution) suggèrent des limites quant à l’efficacité des allégations nutritionnelles. ● La gestion des externalités environnementales négatives de la banane en Guadeloupe est déléguée à des acteurs privés, qui justifient ainsi le bénéfice d’aides publiques permettant de conforter les intérêts de la filière. ● Un cadre d’analyse économique de l’efficience productive est construit pour les productions relevant de l’agriculture écologiquement intensive. Faits et chiffres ● Rôle du coton sur la filière maïs au Burkina Faso Débat ● La réforme de la PAC 2013 Note de lecture ● Qu’est ce que l’agriculture écologiquement intensive