High resolution analysis of DNA copy-number aberrations of chromosomes 8, 13, and 20 in gastric cancers.
DNA copy-number gains of chromosomes 8q, 13q, and 20q are frequently observed in gastric cancers. Moreover gain of chromosome 20q has been associated with lymph node metastasis. The aim of this study was to correlate DNA copy-number changes of individual genes on chromosomes 8q, 13q, and 20q in gastric adenocarcinomas to clinicopathological data. DNA isolated from 63 formalin-fixed and paraffin-embedded gastric adenocarcinoma tissue samples was analyzed by whole-genome microarray comparative genomic hybridization and by multiplex ligation-dependent probe amplification (MLPA), targeting 58 individual genes on chromosomes 8, 13, and 20. Using array comparative genomic hybridization, gains on 8q, 13q, and 20q were observed in 49 (77.8%), 25 (39.7%), and 49 (77.8%) gastric adenocarcinomas, respectively. Gain of chromosome 20q was significantly correlated with lymph node metastases (p = 0.05) and histological type (p = 0.02). MLPA revealed several genes to be frequently gained in DNA copy number. The oncogene c-myc on 8q was gained in 73% of the cancers, while FOXO1A and ATP7B on 13q were both gained in 28.6% of the cases. Multiple genes on chromosome 20q showed gains in more than 60% of the cancers. DNA copy-number gains of TNFRSF6B (20q13.3) and ZNF217 (20q13.2) were significantly associated with lymph node metastasis (p = 0.02) and histological type (p = 0.02), respectively. In summary, gains of chromosomes 8q, 13q, and 20q in gastric adenocarcinomas harbor DNA copy-number gains of known and putative oncogenes. ZNF217 and TNFRSF6B are associated with important clinicopathological variables, including lymph node status.
Buffart
Tineke E
TE
Department of Pathology, VU University Medical Center, PO Box 7057, 1007, Amsterdam, The Netherlands.
van Grieken
Nicole C T
NC
Tijssen
Marianne
M
Coffa
Jordy
J
Ylstra
Bauke
B
Grabsch
Heike I
HI
van de Velde
Cornelis J H
CJ
Carvalho
Beatriz
B
Meijer
Gerrit A
GA
D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D002890:Chromosomes, Human, Pair 20; D002898:Chromosomes, Human, Pair 8; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*; D051438:Syntaxin 16 / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
D053323:Receptors, Tumor Necrosis Factor, Member 6b; C496118:STX16 protein, human; D051438:Syntaxin 16; C505911:TNFRSF6B protein, human; D015534:Trans-Activators; C113698:ZNF217 protein, human
Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):612-20
15701848
Nucleic Acids Res. 2002 Jun 15;30(12):e57
12060695
Int J Cancer. 2003 Jul 10;105(5):724-32
12740925
Acta Pathol Microbiol Scand. 1965;64:31-49
14320675
Mol Pathol. 2003 Oct;56(5):293-8
14514924
Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1230-5
10655513
Cancer Genet Cytogenet. 2000 Mar;117(2):97-103
10704677
Cell Oncol. 2007;29(1):73-5
17429145
J Pathol. 2005 Mar;205(4):514-21
15685687
Eur J Cell Biol. 1998 Mar;75(3):223-31
9587053
BMC Genomics. 2007 Oct 01;8:345
17908304
Nature. 1998 Dec 17;396(6712):699-703
9872321
Mod Pathol. 2004 Nov;17(11):1328-37
15154013
Gastroenterology. 1997 May;112(5):1457-65
9136822
Cell Oncol. 2006;28(5-6):283-94
17167181
J Pathol. 2007 Jan;211(1):45-51
17117405
J Pathol. 2003 Jul;200(3):320-6
12845628
Oncogene. 2003 Mar 27;22(12):1872-9
12660823
Cancer Res. 2001 Feb 15;61(4):1250-4
11245413
Anticancer Res. 2003 Jul-Aug;23(4):3353-7
12926075
Gastroenterology. 2002 Oct;123(4):1109-19
12360473
J Pathol. 2000 Nov;192(3):301-6
11054712
Scand J Gastroenterol. 2004 Aug;39(8):766-72
15513363
Cell Oncol. 2007;29(4):351-9
17641418
Am J Clin Oncol. 2008 Feb;31(1):79-83
18376232
Nat Genet. 2005 Jun;37 Suppl:S11-7
15920524
Nat Genet. 2001 Nov;29(3):263-4
11687795
Am J Pathol. 2001 Jun;158(6):1961-7
11395372
Cell Oncol. 2008;30(4):323-35
18607067
CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
15761078
N Engl J Med. 1999 Mar 25;340(12):908-14
10089184
Genes Chromosomes Cancer. 1999 Apr;24(4):299-305
10092127
Cancer Genet Cytogenet. 1998 Nov;107(1):32-6
9809031
Nature. 1998 Dec 17;396(6712):643-9
9872311
Cell Oncol. 2004;26(5-6):307-17
15623941
Am J Pathol. 2001 Feb;158(2):655-62
11159202
Cancer Sci. 2005 Feb;96(2):100-10
15723654
Bioinformatics. 2007 Apr 1;23(7):892-4
17267432
Cell Oncol. 2005;27(1):57-65
15750208