Huang S F, Xiao S, Renshaw A A, Loughlin K R, Hudson T J, Fletcher J A
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Am J Pathol. 1996 Nov;149(5):1565-73.
Various nonrandom chromosomal aberrations have been identified in prostate carcinoma. These aberrations include deletions of several chromosome regions, particularly the chromosome 8 short arm. Large-scale numerical aberrations, reflected in aberrant DNA ploidy, are also found in a minority of cases. However, it is unclear whether prostate carcinomas contain aberrations of certain chromosome regions that are deleted frequently in other common types of cancer. In this study, we performed dual-color fluorescence in situ hybridization on intact nuclei from touch preparations of 16 prostate cancers. Chromosome copy number was determined using pericentromeric probes, whereas potential chromosome arm deletions were evaluated using yeast artificial chromosome (YAC) and P1 probes. Two YAC probes targeted chromosome 8 short arm regions known to be deleted frequently in prostate cancer. Other YACs and P1s were for chromosome regions, including 1p22, 3p14, 6q21, 9p21, and 22q12, that are deletion targets in a variety of cancers although not extensively studied in prostate cancer. Hybridization efficiencies and signal intensities were excellent for both repeat sequence (alpha-satellite) and single, copy (YAC and P1) fluorescence in situ hybridization probes. Of 16 prostate cancers, 11 had clonal aberrations of 1 or more of the 13 chromosome regions evaluated, and 10 cases (62.5%) had 8p deletions, including 4 cases with 8p deletion in virtually all cells and aneuploidy in only a subset of those deleted cells. Deletions at 3p14, 6q21, and 22q12 were identified in 2, 1, and 1 case, respectively, and each of those cases had a similarly sized cell population with 8p deletion. These studies confirm 8p deletion in the majority of prostate carcinomas. 8p deletions appear to be early events in prostate tumorigenesis, often antedating aneuploidy. Fluorescence in situ hybridization strategies incorporating pericentromeric and single-copy regional chromosome probes offer a powerful and efficient means for determining frequency and progression of oncogenetic events in prostate cancer.
在前列腺癌中已发现多种非随机性染色体畸变。这些畸变包括几个染色体区域的缺失,尤其是8号染色体短臂。少数病例中也发现了反映在异常DNA倍体中的大规模数值畸变。然而,尚不清楚前列腺癌是否含有在其他常见癌症类型中频繁缺失的某些染色体区域的畸变。在本研究中,我们对16例前列腺癌触摸涂片的完整细胞核进行了双色荧光原位杂交。使用着丝粒周围探针确定染色体拷贝数,而使用酵母人工染色体(YAC)和P1探针评估潜在的染色体臂缺失。两个YAC探针靶向已知在前列腺癌中频繁缺失的8号染色体短臂区域。其他YAC和P1探针针对染色体区域,包括1p22、3p14、6q21、9p21和22q12,这些区域是多种癌症中的缺失靶点,尽管在前列腺癌中尚未进行广泛研究。对于重复序列(α-卫星)和单拷贝(YAC和P1)荧光原位杂交探针,杂交效率和信号强度都非常好。在16例前列腺癌中,11例在评估的13个染色体区域中的1个或多个区域存在克隆畸变,10例(62.5%)存在8p缺失,其中4例几乎所有细胞都有8p缺失,且只有一部分缺失细胞为非整倍体。分别在2例、1例和1例中发现了3p14、6q21和22q12的缺失,并且这些病例中的每一例都有一个大小相似的细胞群体存在8p缺失。这些研究证实了大多数前列腺癌中存在8p缺失。8p缺失似乎是前列腺肿瘤发生中的早期事件,通常早于非整倍体出现。结合着丝粒周围和单拷贝区域染色体探针的荧光原位杂交策略为确定前列腺癌中致癌事件的频率和进展提供了一种强大而有效的方法。