Heterogeneous subgroups in human neuroblastoma for clinically relevant risk stratification.
Neuroblastoma is a heterogeneous tumor and that may have a favorable or unfavorable prognosis. In Japan, a nation-wide neuroblastoma mass-screening (MS) project assessed 6-month-old infants between 1985 and 2003, and almost all neuroblastomas, including regressing or maturing tumors were thought to be detected in this period. To evaluate the heterogeneity of neuroblastoma subgroups, we analyzed patients with neuroblastoma who had been diagnosed during this period. The clinical courses of 4,209 patients with neuroblastoma, including 1,560 MS detected patients, whose tumors had been diagnosed between 1971 and 1995 were registered. The 2,520 cases registered between 1985 and 1995 were compared to 1,050 cases registered between 1971 and 1980 and analyzed by a multi-gene target model to determine the age distribution of neuroblastoma incidence. We hypothesized that three target genes were responsible for the progression of neuroblastoma: one pair of tumor suppressor gene alleles, one oncogene, and one gene controlling regression/differentiation. This simulation study revealed that the age distribution at initial diagnosis of neuroblastoma was divided into four groups based on post-fertilization age: 20-40, 40-50, 60-90, and 160-200 weeks. Since neuroblatoma in the first group occurred prenatal, post-natal clinical neuroblastoma can be classified into three age groups: 0-6 months, 1-2 years, and 3-4 years. The 0- to 6-month group consisted of mostly benign tumors, and the two older groups had predominantly malignant phenotypes. Our proposed model could explain qualitatively the distribution of neuroblastoma consisting of one subgroup with a favorable prognosis and two subgroups with unfavorable prognosis. For clinically relevant risk stratification, an age cutoff should be considered by the age distribution of these heterogeneous subgroups.
Hiyama
Eiso
E
Natural Science Center for Basic Research and Development, Hiroshima University, 1-2-3, Kasumi, Hiroshima 734-8551, Japan. eiso@hiroshima-u.ac.jp
Yamaoka
Hiroaki
H
Kondo
Satoshi
S
Yoneda
Akihiro
A
Tajiri
Tatsuro
T
Fukuzawa
Masahiro
M
Sugiyama
Masahiko
M
Hayashi
Yutaka
Y
Sasaki
Fumiaki
F
Ohtaki
Megu
M
D017677:Age Distribution; D002675:Child, Preschool; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D007223:Infant; D007564:Japan / Q000453:epidemiology; D008403:Mass Screening / Q000379:methods*; D009010:Monte Carlo Method; D009447:Neuroblastoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D010641:Phenotype; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
Cancer. 2001 Nov 1;92(9):2451-61
11745303
Science. 1984 Jun 8;224(4653):1121-4
6719137
J Clin Oncol. 2005 Sep 20;23(27):6443-4
16116157
Cancer Lett. 2005 Oct 18;228(1-2):257-66
16024170
Nat Med. 1995 Mar;1(3):249-55
7585042
Jpn J Cancer Res. 1992 Feb;83(2):159-64
1555997
Cancer. 2001 Nov 15;92(10):2699-708
11745206
Lancet Oncol. 2003 Aug;4(8):472-80
12901961
Genes Chromosomes Cancer. 2000 Oct;29(2):89-95
10959087
J Pediatr Surg. 1990 Oct;25(10):1095-9
2262866
Pediatr Blood Cancer. 2007 Feb;48(2):245-6; author reply 247
16652345
Pediatr Surg Int. 2004 Jan;20(1):33-8
14691637
Br J Cancer. 1954 Mar;8(1):1-12
13172380
Med Pediatr Oncol. 2001 Jan;36(1):67-74
11464909
J Clin Oncol. 2005 Aug 1;23 (22):5205-10
16051962
N Engl J Med. 2002 Apr 4;346(14):1047-53
11932471
Nat Rev Cancer. 2003 Mar;3(3):203-16
12612655
J Clin Oncol. 2005 Sep 20;23(27):6459-65
16116153
J Clin Oncol. 2000 Mar;18(6):1260-8
10715296
J Clin Oncol. 2002 Mar 1;20(5):1209-14
11870162
Cancer. 1996 Aug 1;78(3):532-41
8697401
Hiroshima J Med Sci. 2005 Mar;54(1):9-20
15847060
Eur J Cancer. 1997 Oct;33(12):1932-6
9516827
Cancer Res. 1971 Dec;31(12):2098-103
5120301
J Natl Cancer Inst. 1978 Jul;61(1):49-52
276637
Oncogene. 2005 Nov 24;24(53):7902-12
16103881