DNA Copy Number Alterations in Flat Colorectal Adenomas
Q.J.M. Voorham1, B. Carvalho1, A.J. Spiertz2, N.C.T. van Grieken1, H.I. Grabsch3, B.
Rembacken4, M. Kliment5, M.A. van de Wiel6, B. Ylstra1, A.P. de Bruïne2, C.J.J.
Mulder7, M. van Engeland2, G.A. Meijer1
1Dept
of Pathology, VU University Medical Center, Amsterdam, The Netherlands
of Pathology, GROW-School for Oncology and Developmental Biology,
Maastricht University Medical Center, Maastricht, The Netherlands
3Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of
Leeds, UK
4Centre for Digestive Diseases, Leeds General Infirmary, Leeds, UK
5Gastroenterology, Hospital Vitkovice, Ostrava, Czech Republic
6Dept of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam,
The Netherlands
7Dept of Gastroenterology, VU University Medical Center, Amsterdam, The
Netherlands
2Dept
Flat colorectal adenomas are associated with an aggressive clinical behaviour. In
literature it is described that these lesions have a different molecular pathogenesis
than regular polypoid-shaped lesions. Although a number of studies have
investigated molecular alterations (such as mutations and methylation) still little is
known about the tumourigenisis of these lesions. The aim of the present study was to
identify, based on high resolution genome wide DNA copy number profiling,
chromosomal regions that differ between flat and polypoid adenomas and could be
linked to the two different phenotypes.
Formalin-fixed paraffin-embedded (FFPE) material of 27 polypoid and 55 flat
adenomas (classified according to the Paris classification) was isolated and analyzed
by genome wide array comparative genomic hybridization (Agilent, 180K array). DNA
copy number profiles were evaluated and correlated to the different phenotypes.
Preliminary analysis of the data showed that overall all adenomas showed little
chromosomal aberrations, 30 of the 82 adenomas (36.5%) showed less then 1%
aberrant probes. Of the lesions that showed aberrations the most frequent ones were
losses on chromosomes 1p and 18 and gains on chromosomes 7, 8, 9, 12, 13, 20
and X in both types of adenomas. For these regions no significant difference were
found.
However, the proportion of tumours with less then 1% aberrant probes was higher in
flat adenomas when compared to polypoid adenomas, 23 out of 55 (42%) and 7 out
27 (26%), respectively (P = 0.01). Chromosomal regions found to be significantly
different between polypoid and flat lesions were 3p12.3, 8p11.23, 14q32.33, 16p12.3,
17q12 and 21q11.2. (FDR<0.1).
Overall flat and polypoid adenomas are showing the same aberrations. Flat
adenomas had significantly more profiles with little chromosomal aberrations. The
regions 3p12.3, 8p11.23, 14q32.33, 16p12.3, 17q12 and 21q11.2 were significantly
different between the two groups (FDR<0.1). Further investigations are warranted to
uncover which genes located on these regions are involved in the different biological
mechanisms leading to the different phenotypes of these lesions.