Postma C, Hermsen M A J A, Coffa J, Baak J P A, Mueller J D, Mueller E, Bethke B, Schouten J P, Stolte M, Meijer G A
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
J Pathol. 2005 Mar;205(4):514-21. doi: 10.1002/path.1733.
Flat adenomas are flat or slightly elevated dysplastic lesions of the colorectal mucosa, mostly with a tubular architecture. Compared with polypoid adenomas of similar size, flat adenomas show a higher frequency of high-grade dysplasia and rapid submucosal invasion. The aim of this study was to survey whether flat colorectal lesions differ in their pattern of chromosomal aberrations from their polypoid counterparts. Six flat adenomas and 12 flat carcinomas were analysed by comparative genomic hybridization (CGH) and the pattern of chromosomal aberrations was compared with a previously published series of 112 polypoid adenomas and 82 polypoid carcinomas. In addition, multiplex ligation-dependent probe amplification (MLPA) for identifying DNA copy number changes of 25 individual genes on chromosome 20 was performed on 14 flat and 15 polypoid tumours. With CGH, flat adenomas showed on average 1.8 gains (range 1-4) and 3.2 losses (range 0-4), and the flat carcinomas 4.5 gains (range 0-8) and 3.5 losses (range 1-6). In both adenomas and carcinomas, high frequencies of 20q gain (83% and 92%, respectively) and 18q loss (83% and 92%, respectively) were found. This correlation between 20q gain and 18q loss had previously been observed in a subgroup of polypoid colorectal tumours. Both flat and polypoid colorectal tumours with 20q gains by CGH showed similar patterns of copy number ratios for the individual genes tested. TOP1, BCL2L1, and E2F1 had median copy number ratios of 2 or higher, while ZNF217 had a ratio around 3. In conclusion, flat adenomas and carcinomas of the large intestine show a similar pattern of chromosomal aberrations to that observed in a specific subgroup of polypoid lesions. The transcription factor ZNF217 is an important candidate for driving the 20q gain.
扁平腺瘤是结直肠黏膜的扁平或轻度隆起的发育异常病变,大多具有管状结构。与大小相似的息肉状腺瘤相比,扁平腺瘤的高级别发育异常频率更高,且黏膜下侵袭迅速。本研究的目的是调查结直肠扁平病变与息肉状病变在染色体畸变模式上是否存在差异。通过比较基因组杂交(CGH)分析了6个扁平腺瘤和12个扁平癌,并将染色体畸变模式与先前发表的112个息肉状腺瘤和82个息肉状癌系列进行了比较。此外,对14个扁平肿瘤和15个息肉状肿瘤进行了多重连接依赖探针扩增(MLPA),以鉴定20号染色体上25个单个基因的DNA拷贝数变化。通过CGH,扁平腺瘤平均有1.8个增益(范围1 - 4)和3.2个缺失(范围0 - 4),扁平癌有4.5个增益(范围0 - 8)和3.5个缺失(范围1 - 6)。在腺瘤和癌中,均发现20q增益(分别为83%和92%)和18q缺失(分别为83%和92%)的高频率。这种20q增益与18q缺失之间的相关性先前在息肉状结直肠肿瘤的一个亚组中已观察到。通过CGH检测到有20q增益的扁平及息肉状结直肠肿瘤,在所检测的单个基因的拷贝数比值模式上相似。TOPI、BCL2L1和E2F1的中位拷贝数比值为2或更高,而ZNF217的比值约为3。总之,大肠扁平腺瘤和癌的染色体畸变模式与在息肉状病变的特定亚组中观察到的相似。转录因子ZNF217是驱动20q增益的重要候选因子。