A comparison of the genetic pathways involved in the pathogenesis of three types of colorectal cancer
A comparison of the genetic pathways involved in the pathogenesis of three types of colorectal cancer
复制标题
三种结直肠癌发病机制的基因通路比较
作者：
I. Tomlinson;M. Ilyas;V. Johnson;Andrew Davies;G. Clark;I. Talbot;W. Bodmer
为探讨三种类型结直肠癌发病的遗传途径：散发性无复制错误结直肠癌(−)32例，散发性复制错配+结直肠癌(23例)和溃疡性结肠炎相关结直肠癌(UCACR16例)，研究了等位基因丢失(杂合性缺失，LOH)的模式。在与已知或推测的抑癌基因相近的10个微卫星标记上，对每个肿瘤进行等位基因缺失评估：apc(5q21-q22)；dcc(18q21.1)；1p35-p36；p16(9p21)；22q；8p；E-cad(16q22.1)；β-catenin(3p22-p21.3)；rb1(13q14.1-q14.2)；以及人类白细胞抗原。总体而言，DCC(42%)、p16(38%)、22q(37%)、1p35-p36(34%)和APC(31%)等位基因缺失的频率较高(>；30%)，而RB1(16%)和E-cadherin(13%)附近的等位基因缺失频率(<；20%)较低(<；20%)。β-连环蛋白、人类白细胞抗原和8P基因附近的杂合性缺失发生率为20%~30%。等位基因丢失的总体频率在三个肿瘤组中没有差异，但在个别基因座上出现了一些差异。RER+肿瘤中1p35-36的LOH频率明显高于RER−肿瘤。该位点的等位基因丢失也与更高级的Dukes‘s分期有关。此外，与−+肿瘤相比，ReR+肿瘤在p16的等位基因丢失频率更高。散发性结直肠癌的LOH频率与UCACRC的LOH频率在任何一个基因座上均无显著差异。配对分析显示APC区LOH与DCC、22P区LOH与P53过表达呈负相关。因此，在RER+和RER−癌的突变谱之间可能存在特定的差异，但这些癌症和UCACC的潜在遗传途径之间存在很大程度的重叠。©1998 John Wiley&Sons，Ltd.
Patterns of allele loss (loss of heterozygosity, LOH) have been studied in order to investigate the genetic pathways involved in the pathogenesis of three types of colorectal cancer (CRC): sporadic CRC without replication errors (RER−) (32 cases); sporadic RER+ CRC (23 cases); and ulcerative colitis‐associated CRC (UCACRC) (16 cases). Each tumour was assessed for allele loss at ten microsatellite markers which map close to known or putative tumour‐suppressor genes: APC (5q21–q22); DCC (18q21.1); 1p35–p36; p16 (9p21); 22q; 8p; E‐cadherin (16q22.1); β‐catenin (3p22–p21.3); RB1 (13q14.1–q14.2); and HLA. Overall, high frequencies of allele loss (>30 per cent) were found near DCC (42 per cent), p16 (38 per cent), 22q (37 per cent), 1p35–p36 (34 per cent) and APC (31 per cent), and low frequencies (<20 per cent) near RB1 (16 per cent) and E‐cadherin (13 per cent). LOH near β‐catenin, HLA, and on 8p occurred at frequencies between 20 and 30 per cent. The overall frequency of allele loss did not differ among the three tumour groups, but some variation was seen at individual loci. There was a significantly higher frequency of LOH at 1p35–36 in RER+ tumours compared to RER− tumours. Allele loss at this site was also associated with a more advanced Dukes' stage at presentation. In addition, RER− tumours showed a higher frequency of allele loss at p16 than RER+ tumours. No significant difference existed at any locus between the frequency of LOH in sporadic CRC and in UCACRC. Pairwise analysis showed a negative association between LOH at APC and DCC, and between LOH at chromosome 22p and p53 overexpression. Thus, there may be specific differences between the mutation spectra of RER+ and RER− CRCs, but there are large degrees of overlap among the underlying genetic pathways of these cancers and UCACRCs. © 1998 John Wiley & Sons, Ltd.
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影响因子：
29.4
作者：
BRENTNALL, TA;CRISPIN, DA;BURMER, GC
通讯作者：
BURMER, GC
影响因子：
29.4
作者：
Mark Redston;N. Papadopoulos;Carlos Caldas;K. Kinzler;Scott E. Kern
通讯作者：
Mark Redston;N. Papadopoulos;Carlos Caldas;K. Kinzler;Scott E. Kern
影响因子：
16.2
作者：
BURMER, GC;CRISPIN, DA;RABINOVITCH, PS
通讯作者：
RABINOVITCH, PS
影响因子：
11.2
作者：
L. Tarmin;Jing Yin;N. Harpaz;M. Kozam;Jeroen Noordzij;Lilian B. Antonio;H. Jiang;O. Chan;K. Cymes;S. Meltzer
通讯作者：
L. Tarmin;Jing Yin;N. Harpaz;M. Kozam;Jeroen Noordzij;Lilian B. Antonio;H. Jiang;O. Chan;K. Cymes;S. Meltzer
影响因子：
56.9
作者：
PAPADOPOULOS, N;NICOLAIDES, NC;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B