Top

Pediatric Surgery International

Published in:

01-11-2009 | Original Article

Evaluation of genes identified by microarray analysis in favorable neuroblastoma

Authors: Naomi Kamei, Keiko Hiyama, Hiroaki Yamaoka, Arata Kamimatsuse, Yoshiyuki Onitake, Taijiro Sueda, Eiso Hiyama

Published in: Pediatric Surgery International | Issue 11/2009

Abstract

Purpose

The biological heterogeneity of neuroblastoma results in a varied outcome ranging from spontaneous regression to fatal tumor progression. Microarray expression profiling and genetic polymorphism arrays may help identify key genes that differ in aggressive neuroblastomas from those observed in tumors associated with a favorable outcome.

Methods

Total RNA was extracted from 16 neuroblastomas obtained from patients who subsequently died of the disease and from 16 favorable neuroblastomas and analyzed using a human whole genome oligomicroarray (55K CodeLink). Genes overexpressed in favorable tumors were subsequently analyzed in 121 neuroblastoma tumors obtained before chemotherapy using real-time RT-PCR. And among these cases, expression levels of these genes were also analyzed in 20 tumors obtained after chemotherapy.

Results

Oligomicroarray analysis revealed the overexpression of 283 genes in favorable tumors that were associated with either regressing or maturing tumors. Three candidate genes, including DHRS3, NROB1, and CYP26A1, were selected that were significantly overexpressed in favorable tumors by quantitative real-time RT-PCR (P < 0.01). No cases with overexpression of all three genes showed poor outcomes. In 20 post-chemotherapeutic tumors, the expression levels of these genes increased in the cases where patients survived but decreased in the fatal cases.

Conclusions

Using microarray expression profiling, we identified genes that exhibit altered gene expression in neuroblastoma tumors associated with a favorable outcome. These candidates warrant further study for use in risk assessment and/or as therapeutic targets in neuroblastoma.

Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3(3):203–216CrossRefPubMed

Westermann F, Schwab M (2002) Genetic parameters of neuroblastomas. Cancer Lett 184(2):127–147CrossRefPubMed

Hiyama E, Hiyama K, Nishiyama M, Reynolds CP, Shay JW, Yokoyama T (2003) Differential gene expression profiles between neuroblastomas with high telomerase activity and low telomerase activity. J Pediatr Surg 38(12):1730–1734CrossRefPubMed

Hiyama E, Hiyama K, Yamaoka H, Sueda T, Reynolds CP, Yokoyama T (2004) Expression profiling of favorable and unfavorable neuroblastomas. Pediatr Surg Int 20(1):33–38CrossRefPubMed

Hiyama E, Hiyama K (2002) Clinical application of microarrays as a tool of understanding cancer biology. In: Cancro MP (ed) Recent Res Develop Cancer, vol 4. Transworld Research Network, Kerala, India, pp 675–692

Takita J, Ishii M, Tsutsumi S, Tanaka Y, Kato K, Toyoda Y, Hanada R, Yamamoto K, Hayashi Y, Aburatani H (2004) Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma. Genes Chromosomes Cancer 40(2):120–132CrossRefPubMed

Komatsu M, Hiyama K, Tanimoto K, Yunokawa M, Otani K, Ohtaki M, Hiyama E, Kigawa J, Ohwada M, Suzuki M, Nagai N, Kudo Y, Nishiyama M (2006) Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers. Mol Cancer Ther 5(3):767–775CrossRefPubMed

Hiyama K, Otani K, Ohtaki M, Satoh K, Kumazaki T, Takahashi T, Mitsui Y, Okazaki Y, Hayashizaki Y, Omatsu H, Noguchi T, Tanimoto K, Nishiyama M (2005) Differentially expressed genes throughout the cellular immortalization processes are quite different between normal human fibroblasts and endothelial cells. Int J Oncol 27(1):87–95PubMed

Brodeur GM, Seeger RC, Barrett A, Berthold F, Castleberry RP, D’Angio G, De Bernardi B, Evans AE, Favrot M, Freeman AI et al (1988) International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma. J Clin Oncol 6(12):1874–1881PubMed

10.

Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B, Stram DO, Gerbing RB, Lukens JN, Matthay KK, Castleberry RP (1999) The International Neuroblastoma Pathology Classification (the Shimada system). Cancer 86(2):364–372CrossRefPubMed

11.

Sawaguchi S, Kaneko M, Uchino J, Takeda T, Iwafuchi M, Matsuyama S, Takahashi H et al (1990) Treatment of advanced neuroblastoma with emphasis on intensive induction chemotherapy: a report from the Study Group of Japan. Cancer 66:1879–1887CrossRefPubMed

12.

Abu-Abed S, Dolle P, Metzger D, Wood C, MacLean G, Chambon P, Petkovich M (2003) Developing with lethal RA levels: genetic ablation of Rarg can restore the viability of mice lacking Cyp26a1. Development 130(7):1449–1459CrossRefPubMed

13.

Niederreither K, Abu-Abed S, Schuhbaur B, Petkovich M, Chambon P, Dolle P (2002) Genetic evidence that oxidative derivatives of retinoic acid are not involved in retinoid signaling during mouse development. Nat Genet 31(1):84–88PubMed

14.

De Marco P, Merello E, Mascelli S, Raso A, Santamaria A, Ottaviano C, Calevo MG, Cama A, Capra V (2006) Mutational screening of the CYP26A1 gene in patients with caudal regression syndrome. Birth Defects Res A Clin Mol Teratol 76(2):86–95CrossRefPubMed

Title: Evaluation of genes identified by microarray analysis in favorable neuroblastoma
Authors: Naomi Kamei
Keiko Hiyama
Hiroaki Yamaoka
Arata Kamimatsuse
Yoshiyuki Onitake
Taijiro Sueda
Eiso Hiyama
Publication date: 01-11-2009
Publisher: Springer-Verlag
Published in: Pediatric Surgery International / Issue 11/2009
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-009-2448-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Evaluation of genes identified by microarray analysis in favorable neuroblastoma

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 11/2009

Treves’ field pouch hernia: our experience and literature review

Collis–Nissen fundoplication using a computer-powered right angle linear cutting stapler in children

Impact of rikkunshito, an herbal medicine, on delayed gastric emptying in profoundly handicapped patients

Radiographic signs predictive of success of hydrostatic reduction of intussusception

Hirschsprung’s disease patients diagnosed at over 15 years of age: an analysis of a Japanese nationwide survey

Spontaneous sutureless closure of the abdominal wall defect in gastroschisis using a commercial wound retractor system