TY - JOUR
T1 - Evaluation of cancer-associated DNA copy number events in colorectal (advanced) adenomas
AU - Carvalho, Beatriz
AU - Diosdado, Begona
AU - Droste, Jochim S. Terhaar Sive
AU - Bolijn, Anne S.
AU - Komor, Malgorzata A.
AU - de Wit, Meike
AU - Bosch, Linda J. W.
AU - van Burink, Myrthe
AU - Dekker, Evelien
AU - Kuipers, Ernst J.
AU - Coupe, Veerle M. H.
AU - van Grieken, Nicole C. T.
AU - Fijneman, Remond J. A.
AU - Meijer, Gerrit A.
PY - 2018
Y1 - 2018
N2 - About 5% of colorectal adenomas are estimated to progress to colorectal cancer. However, it is important to identify which adenomas actually carry a high risk of progression, because these serve as intermediate endpoints, for example, in screening programs. In clinical practice, adenomas with a size of 10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high risk, although solid evidence for this classification is lacking. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression. We set out to determine the prevalence of cancerassociated events (CAE) in advanced and nonadvanced adenomas. DNA copy number analysis was performed on archival tissues from three independent series of, in total, 297 adenomas (120 nonadvanced and 177 advanced) using multiplex ligation-dependent probe amplification or low-coverage whole-genome DNA sequencing. Alterations in two or more CAEs were considered to mark adenomas as high risk. Two or more CAEs were overall present in 25% (95% CI, 19.0-31.8) of advanced adenomas; 23% (11/48), 36% (12/33), and 23% (22/96) of the advanced adenomas in series 1, 2, and 3, respectively, and 1.7% (1/58) and 4.8% (3/62) of the nonadvanced adenomas, in series 1 and 2, respectively. The majority of advanced adenomas do not show CAEs, indicating that only a subset of these lesions is to be considered high risk. Nonadvanced adenomas have very low prevalence of CAEs, although those with CAEs should be considered high risk as well. Specific DNA copy number alterations may better reflect the true progression risk than the advanced adenoma phenotype.
AB - About 5% of colorectal adenomas are estimated to progress to colorectal cancer. However, it is important to identify which adenomas actually carry a high risk of progression, because these serve as intermediate endpoints, for example, in screening programs. In clinical practice, adenomas with a size of 10 mm, villous component and/or high-grade dysplasia, called advanced adenomas, are considered high risk, although solid evidence for this classification is lacking. Specific DNA copy number changes are associated with adenoma-to-carcinoma progression. We set out to determine the prevalence of cancerassociated events (CAE) in advanced and nonadvanced adenomas. DNA copy number analysis was performed on archival tissues from three independent series of, in total, 297 adenomas (120 nonadvanced and 177 advanced) using multiplex ligation-dependent probe amplification or low-coverage whole-genome DNA sequencing. Alterations in two or more CAEs were considered to mark adenomas as high risk. Two or more CAEs were overall present in 25% (95% CI, 19.0-31.8) of advanced adenomas; 23% (11/48), 36% (12/33), and 23% (22/96) of the advanced adenomas in series 1, 2, and 3, respectively, and 1.7% (1/58) and 4.8% (3/62) of the nonadvanced adenomas, in series 1 and 2, respectively. The majority of advanced adenomas do not show CAEs, indicating that only a subset of these lesions is to be considered high risk. Nonadvanced adenomas have very low prevalence of CAEs, although those with CAEs should be considered high risk as well. Specific DNA copy number alterations may better reflect the true progression risk than the advanced adenoma phenotype.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85049580524&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29685877
U2 - 10.1158/1940-6207.CAPR-17-0317
DO - 10.1158/1940-6207.CAPR-17-0317
M3 - Article
C2 - 29685877
VL - 11
SP - 403
EP - 411
JO - Cancer Prevention Research
JF - Cancer Prevention Research
SN - 1940-6207
IS - 7
ER -