Pronounced chromosomal instability and multiple gene amplifications characterize ulcerative colitis-associated colorectal carcinomas.
Patients with ulcerative colitis have a significantly increased lifetime risk for the development of colorectal carcinomas. While genetic and genomic changes during carcinogenesis have been thoroughly studied in sporadic colorectal cancers, less is known about ulcerative colitis-associated colorectal carcinomas. The aim of this study was to extend the identification of specific genomic imbalances to ulcerative colitis-associated colorectal carcinomas and to establish a comprehensive map of DNA gains and losses by investigating 23 tumor specimens from 23 patients. The molecular cytogenetic characterization was performed using comparative genomic hybridization; immunohistochemistry was used to measure proliferative activity and laminin-5 expression as a marker for invasiveness. The results indicate that these tumors are invariably aneuploid, with a high proliferative activity and increased invasive potential. The average number of copy alterations correlates with increased cyclin A levels (P=0.044), which is an independent predictor of risk of carcinoma development in ulcerative colitis. Despite severe genetic instability, the general pattern of specific chromosomal aberrations that defines sporadic colorectal carcinomas is maintained in ulcerative colitis-associated malignancies. High-level copy number increases (amplifications) are dispersed throughout the genome. Strikingly, these amplifications are much more frequent than in sporadic carcinomas and map to chromosomal regions that have not been described before.
Habermann
Jens K
JK
Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 50, Room 1408, 50 South Drive, Bethesda, MD 20892-8010, USA.
Upender
Madhvi B
MB
Roblick
Uwe J
UJ
Krüger
Stefan
S
Freitag
Sandra
S
Blegen
Harald
H
Bruch
Hans Peter
HP
Schimmelpenning
Hendrik
H
Auer
Gert
G
Ried
Thomas
T
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D022981:Allelic Imbalance / Q000235:genetics; D043171:Chromosomal Instability / Q000235:genetics*; D002869:Chromosome Aberrations; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003110:Colonic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics; D004171:Diploidy; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization; D012004:Rectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D013997:Time Factors
D004273:DNA, Neoplasm