Two novel regions of interstitial deletion on chromosome 8p in colorectal cancer
Two novel regions of interstitial deletion on chromosome 8p in colorectal cancer
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DOI：
10.1038/sj.onc.1202340
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发表时间：
1999-01-21
期刊：
影响因子：
8
通讯作者：
Morton, DG
中科院分区：
文献类型：
--
作者：
Chughtai, SA;Crundwell, MC;Morton, DG
我们使用11个微卫星标记研究了70例结直肠癌和11例结肠腺瘤中8号染色体的间质缺失，其中包括8个跨越染色体8 p（p11.2-p12）的着丝粒区域。在38例（54%）癌症和4例（36%）腺瘤中观察到等位基因丢失或不平衡，其中28例（40%）癌症有8p11.2-p12缺失。在该区域内发现了两个不同且独立的间质损失区域。荧光原位杂交，使用α！在4个肿瘤中进行了8 p着丝粒的卫星重复探针和P1区域的两个探针，证明等位基因不平衡。在所有四种肿瘤中证实了局部杂合缺失，十一种（16%）癌症在区域ANK-1至D8 S255（P1）中具有局部缺失，并且另外十一种（16%）癌症在由标记D8 S87至D8 S259（P2）限定的区域中具有较不好的局部缺失。在另外六种（9%）肿瘤中鉴定了两个着丝粒基因座的缺失，这两个缺失区域的功能意义与原发性和继发性肿瘤特征的相关性。孤立的P2缺失与“早期”T1癌相关（2 p = 0.0002），并且在3/11的腺瘤中也被确定。相反，P1基因座的间质缺失在“局部浸润性”T3/4癌中更常见（2 p = 0.015），并且孤立的P1缺失也与肝转移的存在相关（2 p = 0.016）。我们的数据提供了证据，至少有两个基因在8p11.2-p12区域，突变，其中可能赋予不同的和独立的作用，在结直肠癌的发病机制。
We have investigated interstitial deletions of chromosome 8 in 70 colorectal carcinomas and 11 colonic adenomas using 11 microsatellite markers, including eight spanning the centromeric region of chromosome 8p (p11.2-p12). Allelic loss or imbalance was observed in 38 (54%) cancers and four (36%) adenomas, Twenty-eight (40%) of the cancers had deletions of 8p11.2-p12. Two distinct and independent regions of interstitial loss were found within this region. Fluorescent in situ hybridization, using an alpha! satellite repeat probe to the centromere of 8p and two probes to the P1 region, was performed in four tumours that demonstrated allelic imbalance. Localized heterozygous deletions were confirmed in all four tumours, Eleven (16%) cancers had localized deletion in the region ANK-1 to D8S255 (P1) and a further eleven (16%) cancers had a less well localized deletion in the region defined by the markers D8S87 to D8S259 (P2), Loss of both centromeric loci was identified in a further six (9%) tumours, A functional significance for these two deletion regions was sought by correlation with primary and secondary tumour characteristics. Isolated P2 deletion was associated with 'early' T1 cancers (2p = 0.0002), and were also identified in 3/11 adenomas, Conversely, interstitial deletions of the P1 locus were more frequently seen in 'locally invasive' T3/4 cancers (2p = 0.015), and isolated P1 deletions were also associated with the presence of liver metastases (2p = 0.016). Our data provide evidence of at least two genes within the 8p11.2-p12 region, mutations in which may confer different and independent roles in the pathogenesis of colorectal cancer.