Fearon E R, Hamilton S R, Vogelstein B
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Science. 1987 Oct 9;238(4824):193-7. doi: 10.1126/science.2889267.
The clonal composition of human colorectal tumors was studied by means of restriction fragment length polymorphisms (RFLPs). First, X-linked RFLPs were used to examine the pattern of X chromosome inactivation in colorectal tumors of females. All 50 tumors examined showed monoclonal patterns of X chromosome inactivation; these tumors included 20 carcinomas as well as 30 adenomas of either familial or spontaneous type. Second, RFLPs of autosomes were used as clonal markers to detect the somatic loss or gain of specific chromosomal sequences in colorectal tumors. Among other changes, it was found that somatic loss of chromosome 17p sequences occurred in over 75 percent of the carcinomas examined, but such loss was rare in adenomas. These data support a monoclonal origin for colorectal neoplasms, and suggest that a gene on the short arm of chromosome 17 may be associated with progression from the benign to the malignant state.
采用限制性片段长度多态性(RFLP)方法研究了人类结肠直肠肿瘤的克隆组成。首先,利用X连锁RFLP检测女性结肠直肠肿瘤中X染色体失活模式。所检测的50个肿瘤均显示出X染色体失活的单克隆模式;这些肿瘤包括20例癌以及30例家族性或散发性腺瘤。其次,利用常染色体的RFLP作为克隆标记,检测结肠直肠肿瘤中特定染色体序列的体细胞性缺失或获得。在其他变化中,发现超过75%的所检测癌中发生了17号染色体短臂序列的体细胞性缺失,但这种缺失在腺瘤中很少见。这些数据支持结肠直肠肿瘤的单克隆起源,并提示17号染色体短臂上的一个基因可能与从良性状态向恶性状态的进展有关。