Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression.
OBJECTIVE
This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon.


METHODS
Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays.


RESULTS
The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q.


CONCLUSIONS
This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.
Carvalho
B
B
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. ga.meijer@vumc.nl
Postma
C
C
Mongera
S
S
Hopmans
E
E
Diskin
S
S
van de Wiel
M A
MA
van Criekinge
W
W
Thas
O
O
Matthäi
A
A
Cuesta
M A
MA
Terhaar Sive Droste
J S
JS
Craanen
M
M
Schröck
E
E
Ylstra
B
B
Meijer
G A
GA
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D055028:Comparative Genomic Hybridization / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins