Kern S E, Fearon E R, Tersmette K W, Enterline J P, Leppert M, Nakamura Y, White R, Vogelstein B, Hamilton S R
Department of Pathology, Johns Hopkins Medical Institution, Baltimore, Md 21205.
JAMA. 1989 Jun 2;261(21):3099-103. doi: 10.1001/jama.261.21.3099.
Clinical and pathological associations with molecular genetic alterations were studied in colorectal carcinomas from 83 patients. Fractional allelic loss, a measure of allelic deletions throughout the genome, and allelic deletions of specific chromosomal arms (the short arm of 17 and long arm of 18) each provided independent prognostic information by multivariate analysis when considered individually with Dukes' classification. Distant metastasis was significantly associated with high fractional allelic loss and with deletions of 17p and 18q. Mutations of ras proto-oncogenes and deletions of 5q had no prognostic importance. Statistically significant associations were also found between allelic losses and a family history of cancer, left-sided tumor location, and absence of extracellular tumor mucin. Allelic deletion analysis thus identified subsets of colorectal carcinoma with increased predilection for distant metastasis and cancer-related death. Further studies may define a subset of genetic alterations that can be used clinically to help assess prognosis.
对83例结直肠癌患者的临床和病理特征与分子遗传学改变之间的关联进行了研究。通过多变量分析,全基因组等位基因缺失分数(衡量全基因组等位基因缺失的指标)以及特定染色体臂(17号染色体短臂和18号染色体长臂)的等位基因缺失,在与Dukes分期单独考虑时,各自都提供了独立的预后信息。远处转移与高全基因组等位基因缺失分数以及17p和18q缺失显著相关。ras原癌基因突变和5q缺失无预后意义。在等位基因缺失与癌症家族史、肿瘤位于左侧以及细胞外肿瘤黏液缺失之间也发现了具有统计学意义的关联。因此,等位基因缺失分析确定了结直肠癌中远处转移和癌症相关死亡倾向增加的亚组。进一步的研究可能会确定一组可在临床上用于帮助评估预后的基因改变。