2p24 Gain region harboring MYCN gene compared with MYCN amplified and nonamplified neuroblastoma: biological and clinical characteristics.
Although the role of MYCN amplification in neuroblastoma is well established, the biological and clinical characteristics of the 2p gain region harboring the MYCN gene remain unclear. The aim of this study was to compare the biological and clinical characteristics of these tumors with MYCN amplified and nonamplified neuroblastoma and to determine their impact on disease outcome. Samples from 177 patients were analyzed by fluorescence in situ hybridization, including MYCN, 1p, 17q, and 11q regions; 2p gain was identified in 25 patients, MYCN amplification in 31, and no amplification in 121 patients. Patients with 2p gain had a significantly worse 5-year event-free survival rate than patients with no MYCN amplified (P < 0.001), and an intermediate 5-year overall survival rate difference existed between the MYCN amplified tumors (P = 0.025) and nonamplified (P = 0.003) groups. All of the 2p gain samples were associated with segmental and/or numerical alterations in the other tested regions. The presence of segmental alterations with or without MYCN amplification was recently found to be the strongest predictor of relapse in a multivariate analysis. The results of the present study suggest that the determination of MYCN gene copy number relative to chromosome 2, when evaluating MYCN status at diagnosis, may help to reveal the underlying genetic pattern of these tumors and better understand their clinical behavior.
Jeison
Marta
M
Ca-Cytogenetic Lab, Schneider Children's Medical Center of Israel, Kaplan St. 14, 49202 Petah Tikva, Israel. martaj@clalit.org.il
Ash
Shifra
S
Halevy-Berko
Gili
G
Mardoukh
Jacques
J
Luria
Drorit
D
Avigad
Smadar
S
Feinberg-Gorenshtein
Galina
G
Goshen
Yacov
Y
Hertzel
Gabriel
G
Kapelushnik
Joseph
J
Ben Barak
Ayelet
A
Attias
Dina
D
Steinberg
Ran
R
Stein
Jerry
J
Stark
Batia
B
Yaniv
Isaac
I
D002648:Child; D002889:Chromosomes, Human, Pair 2; D018572:Disease-Free Survival; D005784:Gene Amplification; D018628:Gene Dosage; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*
C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
Nature. 2008 Oct 16;455(7215):930-5
18724359
N Engl J Med. 1999 Jun 24;340(25):1954-61
10379019
Cancer Genet Cytogenet. 2003 Jan 15;140(2):157-61
12645655
Eur J Cancer. 1997 Sep;33(10):1627-33
9389925
Cancer Genet Cytogenet. 2004 Aug;153(1):10-5
15325088
Cancer Lett. 2005 Oct 18;228(1-2):83-90
15967571
Genes Chromosomes Cancer. 1998 Oct;23(2):116-22
9739014
Int J Cancer. 1999 Feb 9;80(4):630-1
9935168
Med Pediatr Oncol. 2000 Dec;35(6):538-40
11107111
Med Pediatr Oncol. 2001 Jan;36(1):14-9
11464868
J Clin Oncol. 2009 Jan 10;27(2):289-97
19047291
J Clin Oncol. 2003 Jun 1;21(11):2077-84
12775732
Science. 1984 Jun 8;224(4653):1121-4
6719137
J Clin Oncol. 2009 Mar 1;27(7):1026-33
19171713
Oncogene. 2007 Nov 22;26(53):7432-44
17533364
Nucleic Acids Res. 2002 Jun 15;30(12):e57
12060695
Cancer Genet Cytogenet. 2004 Oct 1;154(1):44-51
15381371
Nature. 2008 Oct 16;455(7215):971-4
18923524
Cancer Lett. 2001 Jun 26;167(2):115-23
11369131
Semin Cancer Biol. 1999 Aug;9(4):319-25
10448118
Br J Cancer. 2007 Jul 16;97(2):238-46
17579628
Genes Chromosomes Cancer. 2002 Jul;34(3):313-24
12007192
Cancer Genet Cytogenet. 2003 Feb;141(1):32-42
12581896
Med Pediatr Oncol. 2001 Jan;36(1):83-92
11464912
Cancer Res. 1995 Aug 15;55(16):3471-4
7627947
N Engl J Med. 1985 Oct 31;313(18):1111-6
4047115
J Clin Oncol. 2000 Nov 1;18(21):3604-13
11054433
Clin Cancer Res. 2009 Mar 15;15(6):2085-90
19276282
Proc Natl Acad Sci U S A. 1984 Aug;81(15):4940-4
6589638
J Clin Oncol. 1991 Apr;9(4):581-91
2066755
Clin Cancer Res. 2003 Oct 15;9(13):4835-40
14581355
Am J Pathol. 2008 Jan;172(1):203-14
18165268
Biochem J. 2008 Dec 1;416(2):153-9
18990089
Eur J Cancer. 2004 Dec;40(18):2753-9
15571958
J Pathol. 2002 Dec;198(4):495-501
12434419
J Clin Oncol. 2005 Sep 20;23(27):6459-65
16116153
J Pediatr Surg. 2006 Mar;41(3):560-6
16516635
Nature. 2008 Oct 16;455(7215):967-70
18923523
Cancer Lett. 2005 Oct 18;228(1-2):71-81
15951107
Cancer Res. 1995 Oct 15;55(20):4664-9
7553646
Br J Cancer. 2009 May 5;100(9):1471-82
19401703
Genes Chromosomes Cancer. 2006 Dec;45(12):1130-42
16958102
Nat Rev Cancer. 2003 Mar;3(3):203-16
12612655
Oncogene. 1999 Sep 2;18(35):4948-57
10490829
Cancer. 1999 Jul 15;86(2):364-72
10421273
Cancer. 2006 Sep 15;107(6):1391-9
16917952
N Engl J Med. 2005 Nov 24;353(21):2243-53
16306521
Med Pediatr Oncol. 2000 Dec;35(6):544-6
11107113
Cancer Res. 1995 Nov 15;55(22):5366-9
7585602
N Engl J Med. 1996 Jan 25;334(4):225-30
8531999
J Clin Oncol. 1993 Aug;11(8):1466-77
8336186
Clin Cancer Res. 2003 Jan;9(1):52-8
12538451
Am J Pathol. 1993 May;142(5):1339-46
7684192
Int J Cancer. 2001 Mar 1;91(5):680-6
11267980
J Clin Oncol. 1999 Jul;17(7):2264-79
10561284
Cancer Lett. 2003 Jul 18;197(1-2):75-9
12880963
Virchows Arch. 2008 Jul;453(1):47-55
18574593
Cancer Genet Cytogenet. 2001 Jul 15;128(2):108-13
11463448
Cytogenet Genome Res. 2004;106(1):49-54
15218241
Diagn Mol Pathol. 2005 Mar;14(1):9-16
15714058
PLoS One. 2007 Feb 28;2(2):e255
17327916