Integrative genomic and gene expression analysis of chromosome 7 identified novel oncogene loci in non-small cell lung cancer

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Abstract:

Lung cancer accounts for over a quarter of cancer deaths, with non-small cell lung cancer (NSCLC) accounting for approximately 80% of cases. Several genome studies have been undertaken in both cell models of NSCLC and clinical samples to identify alterations underlying disease behaviour, and many have identified recurring aberrations of chromosome 7. The presence of recurring chromosome 7 alterations that do not span the well-studied oncogenes EGFR (at 7p11.2) and MET (at 7q31.2) has raised the hypothesis of additional genes on this chromosome that contribute to tumourigenesis. In this study, we demonstrated that multiple loci on chromosome 7 are indeed amplified in NSCLC, and through integrative analysis of gene dosage alterations and parallel gene expression changes, we identified new lung cancer oncogene candidates, including FTSJ2, NUDT1, TAF6, and POLR2J. Activation of these key genes was confirmed in panels of clinical lung tumour tissue as compared with matched normal lung tissue. The detection of gene activation in multiple cohorts of samples strongly supports the presence of key genes involved in lung cancer that are distinct from the EGFR and MET loci on chromosome 7.

Le cancer du poumon compte pour le quart des décès dus au cancer et les cancer du poumon à grandes cellules (NSCLC pour « non-small cell lung cancer ») comptent pour environ 80% de ces cas. Plusieurs études génomiques ont été entreprises tant chez des systèmes cellulaires modèles du NSCLC que chez des échantillons cliniques pour identifier les altérations derrière le comportement pathologique. Plusieurs de ces études ont identifié des aberrations récurrentes sur le chromosome 7. La présence d’altérations récurrentes sur le chromosome 7 qui ne chevauchent pas les oncogènes largement étudiés EGFR (à 7p11.2) et MET (à 7q31.2) soulève l’hypothèse que d’autres gènes sur ce chromosome contribueraient à la tumorigénèse. Dans ce travail, les auteurs montrent que de multiples locus sur le chromosome 7 sont effectivement amplifiés chez les NSCLC. Par analyse intégrative des altérations dans le dosage génique et, parallèlement, des changements observés dans l’expression génique, les auteurs ont identifié de nouveaux oncogènes candidats pour le cancer du poumon dont FTSJ2, NUDT1, TAF6 et POLR2J. L’activation de ces gènes clés a été confirmée chez un panel de tissus pulmonaires tumoraux comparés à des tissus pulmonaires normaux correspondants. L’observation d’une activation génique chez de multiples cohortes d’échantillons supporte fortement l’existence de gènes clés impliqués dans le cancer du poumon autres que les loci EGFR et MET sur le chromosome 7.

Document Type: Research Article

Publication date: December 1, 2008

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  • From its inception in 1957, this international cytogenetics journal has catered to the research areas of the members of the Genetics Society of Canada; traditionally, these have included agriculture, entomology, genetics/cytogenetics, and evolutionary mechanisms. The contents of the journal have evolved as contributors developed new technologies and interests. A 20-member Editorial Board is composed of scientists from around the world. Reviews and commentary from respected experts are often featured.
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