Proctor A J, Coombs L M, Cairns J P, Knowles M A
Epithelial Carcinogenesis Laboratory, Marie Curie Research Institute, Oxted, Surrey, UK.
Oncogene. 1991 May;6(5):789-95.
Amplification of several markers which map to chromosome 11q13 was detected by Southern blotting in transitional cell tumours of the urinary bladder. The oncogenes INT2 and HST and the BCL1 locus were co-amplified in 20/97 (20.6%) tumours and the locus-specific minisatellite probe pMS51 (D11S97) detected amplification in 17/97 (17.5%) tumours. The high frequency of heterozygosity (greater than 70%) detected by this latter probe on HaeIII-digested DNAs provided a sensitive means to measure low levels of gene amplification (2-fold) by comparing signals obtained from each allele. A number of probes which map to 11q were used in an attempt to map the region of amplification more precisely. PGA, PGR, STMY, D11Z1 and D11S149 were not amplified in any tumours studied. SEA was amplified in 1/59 tumours and D11S146 in 12/89 tumours. A comparison of the patterns of co-amplification of individual markers in this series of tumours revealed that of the 23 tumours with amplification at this site, 11 had co-amplification of D11S97, D11S146, BCL1, INT2 and HST, 3 had co-amplification of D11S97, BCL1, INT2 and HST, 6 had co-amplification of BCL1, INT2 and HST, 1 had co-amplification of D11S97 and D11S146 and 2 had amplification of D11S97 alone. Based on available linkage data for these markers, this suggests that a putative target gene within this amplicon lies centromeric to BCL1. Amplification at 11q13 showed no correlation with tumour grade or with HER2 amplification.
通过Southern印迹法在膀胱移行细胞肿瘤中检测到几个定位于染色体11q13的标记物的扩增。致癌基因INT2和HST以及BCL1基因座在20/97(20.6%)的肿瘤中共同扩增,位点特异性小卫星探针pMS51(D11S97)在17/97(17.5%)的肿瘤中检测到扩增。用该探针在经HaeIII消化的DNA上检测到的高杂合率(大于70%),为通过比较每个等位基因获得的信号来测量低水平基因扩增(2倍)提供了一种灵敏的方法。使用了一些定位于11q的探针,试图更精确地定位扩增区域。在研究的任何肿瘤中,PGA、PGR、STMY、D11Z1和D11S149均未扩增。SEA在1/59的肿瘤中扩增,D11S146在12/89的肿瘤中扩增。对该系列肿瘤中单个标记物的共同扩增模式进行比较发现,在该位点有扩增的23个肿瘤中,11个有D11S97、D11S146、BCL1、INT2和HST的共同扩增;3个有D11S97、BCL1、INT2和HST的共同扩增;6个有BCL1、INT2和HST的共同扩增;1个有D11S97和D11S146的共同扩增;2个仅有D11S97的扩增。根据这些标记物的现有连锁数据,这表明该扩增子内的一个假定靶基因位于BCL1的着丝粒侧。11q13处的扩增与肿瘤分级或HER2扩增均无相关性。