6533b82afe1ef96bd128b83e
RESEARCH PRODUCT
Segmental chromosomal alterations lead to a higher risk of relapse in infants with MYCN-non-amplified localised unresectable/disseminated neuroblastoma (a SIOPEN collaborative study)
Gaëlle PierronAndrew D.j. PearsonB. De BernardiRuth LadensteinNathalie AugerGian Paolo ToniniMary GerrardCombaretBárbara MarquesK WheelerKlaus BeiskeA F De LacerdaJérôme CouturierJérôme CouturierOlivier DelattreOlivier DelattreJean BénardDeborah A. TweddleGudrun SchleiermacherGudrun SchleiermacherBénédicte BrichardAgnès RibeiroHervé RubieRosa NogueraI.m. AmbrosCastelMosseriKatia MazzoccoNick BownAdela CañeteR. DefferrariCaroline MunzerPeter F. AmbrosJean MichonIsabelle Janoueix-leroseyA. Di CataldoEva VillamónN. Van Roysubject
OncologyCancer Researchmedicine.medical_specialtyPathologyChromosomal AlterationsN-Myc Proto-Oncogene Proteinsegmental chromosome alterationsneuroblastomaNeuroblastomaRecurrenceInternal medicineNeuroblastomamedicineHumansProspective StudiesStage (cooking)Relapse riskProspective cohort studygenomic profileSurvival analysisChromosome AberrationsOncogene ProteinsN-Myc Proto-Oncogene Proteininfantsbusiness.industryInfantNuclear ProteinsGenetics and GenomicsPrognosismedicine.diseaseSurvival AnalysisDoenças GenéticasOncologySegmental Chromosome AlterationsHigh RiskGenomic Profilebusinessdescription
BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials. RESULTS: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival. CONCLUSION: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.
year | journal | country | edition | language |
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2011-12-01 | British Journal of Cancer |