Detection of MYCN Gene Amplification in Neuroblastoma by Fluorescence In Situ Hybridization: A Pediatric Oncology Group Study

Mathew, Prasad; Valentine, Marcus B.; Bowman, Laura C.; Rowe, Susan; Nash, M; Valentine, Virginia; Cohn, Susan L.; Castleberry, Robert P.; Brodeur, Garrett M.; Look, A. Thomas

doi:10.1038/sj.neo.7900146

Cited by 82 publications

(63 citation statements)

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“…In cases 4 and 30, MNA were confirmed by FISH method, however, in all the cases MNA were not confirmed by it. MYCN amplification must be determined by adding the FISH method in these cases (Mathew et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening

et al. 2006

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MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (Po0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; Po0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P ¼ 0.049, P ¼ 0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable.

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Section: Discussionmentioning

confidence: 99%

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening

et al. 2006

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“…In addition, the prevalence of MYCN oncogene amplification, which is an important prognostic factor, was 18%, similar to that of the published clinical series. 2,28 Nineteen percent (n 5 44) of the eligible cases did not respond. However, the age and gender distributions of the respondent and nonrespondent cases were similar.…”

Section: Discussionmentioning

confidence: 99%

Birth‐related characteristics, congenital malformation, maternal reproductive history and neuroblastoma: The ESCALE study (SFCE)

Munzer

Ménégaux

Lacour

et al. 2007

Intl Journal of Cancer

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Since neuroblastoma occurs very early in children's lives, it has been hypothesized that pre-and perinatal factors may play a role in its etiology. This study investigated the role of birth characteristics, congenital malformation and maternal reproductive history in neuroblastoma. The data used were generated by the national population-based case-control study, ESCALE, conducted in France in [2003][2004]. The mothers of 191 neuroblastoma cases and 1,681 controls, frequency-matched by age and gender, were interviewed by telephone, using a standardized questionnaire, on several factors including pregnancy, medical history, lifestyle, childhood medical conditions and exposures. A positive association between congenital malformation and all neuroblastoma cases was observed [Odds ratio (OR) 5 2.2, 95% confidence interval (95% CI): 1.1-4.5]. Congenital malformations were highly associated to neuroblastoma in children aged less than 1 year (OR 5 16.8, 95% CI: 3.1-90), while no association was observed in children aged 1 year or more (OR 5 1.0, 95% CI: 0.3-2.9). A negative association with a maternal history of spontaneous abortions was also found (OR 5 0.6, 95% CI: 0.4-0.9). The results strongly support the hypothesis that congenital anomalies may be associated with neuroblastoma, particularly in infant (less than 1 year of age). ' 2007 Wiley-Liss, Inc.

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“…Fluorescence in situ hybridization, done on diagnostic samples as described previously, was used to determine MYCN amplification status (19). The probe was a cosmid clone from the MYCN genomic locus or a commercially available labeled MYCN probe (Vysis, Inc., Des Plaines, IL).…”

Section: Methodsmentioning

confidence: 99%

Does MYCN Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study

Moreau

McGrady²,

London³

et al. 2006

Clinical Cancer Research

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Purpose: MYCN amplification in neuroblastoma tumor cells is manifested primarily as double minutes (dmins), whereas in cell lines it often appears in the form of homogeneously staining regions (HSR), suggesting that HSRs are associated with a more aggressive tumor phenotype and worse clinical outcome. The aim of this study was to determine whether children with neuroblastoma in which MYCN oncogene amplification is manifested as HSRs at diagnosis have a worse prognosis than those whose tumors exhibit dmins. Experimental Design: A retrospective analysis of primary neuroblastomas analyzed for MYCN amplification by the Children's Oncology Group between 1993 and 2004 was done. Tumors with MYCN amplification were defined as having dmins, HSRs, or both (dmins + HSRs), and associations with currently used risk group stratification variables and patient outcome were assessed. Results: Of the 4,102 tumor samples analyzed, 800 (19.5%) had MYCN amplification. Among the 677 tumors for which the pattern of amplification was known, 629 (92.9%) had dmins, 40 (5.9%) had HSRs, and 8 (0.1%) had dmins + HSRs. Although MYCN amplification is associated with older age, higher stage, and unfavorable histology, whether the amplification occurred as dmins or HSRs did not significantly affect these risk factors. There were no differences in the event-free survival (EFS) or overall survival in patients with MYCN amplification manifested as either dmins or HSRs (5-year EFS, 35 F 3% versus 38 F 15%; P = 0.59). Although the eight patients with dmins + HSRs fared worse than either of the individual subgroups (EFS, 18 F 16% versus 35 F 3% for dmins and 38 F 15% for HSRs), these differences were not significant. Conclusions: MYCN amplification in any form (HSRs or dmins) is associated with a poor outcome.DNA amplification is a mechanism by which a cancer cell acquires multiple copies of part of its genome, enabling it to overexpress oncogenes that confer a selective growth advantage or to acquire resistance to chemotherapeutic agents (1, 2).Gene amplification is most often manifested as paired extrachromosomal self-replicating double-minute chromatin bodies (dmins), which are acentric and atelomeric (3), or as uniformly staining, linearly integrated chromosomal segments called homogenously staining regions (HSR; ref. 4). dmins are commonly seen in primary tumors, whereas HSRs tend to predominate in cultured neoplastic cells (5, 6). HSRs are thought to be formed by integration of multimerized sequences of dmins into chromosomes (7,8). They are considered stable forms of amplification because they provide a faithful mechanism by which the extra copies of the gene can be passed onto the daughter cells. dmins, on the other hand, are considered highly unstable, as they tend to be lost over time either by micronucleation or by uneven distribution into daughter cells (2, 9). The transition from dmins to HSRs is thought to occur through stepwise selection that confers on cells a selective growth advantage, enabling them to survive in culture th...

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Detection of MYCN Gene Amplification in Neuroblastoma by Fluorescence In Situ Hybridization: A Pediatric Oncology Group Study

Cited by 82 publications

References 10 publications

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening

Birth‐related characteristics, congenital malformation, maternal reproductive history and neuroblastoma: The ESCALE study (SFCE)

Does MYCN Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study

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