Krontiris T G, DiMartino N A, Mitcheson H D, Lonergan J A, Begg C, Parkinson D R
Department of Medicine, Hematology/Oncology, Tufts-New England Medical Center, Boston, MA 02111.
Environ Health Perspect. 1987 Dec;76:147-53. doi: 10.1289/ehp.8776147.
A variable tandem repeat (VTR) is responsible for the hyperallelism one kilobase 3' to the human c-Ha-ras-1 (Ha-ras) gene. Thirty-two distinct restriction fragments, comprising 3 allelic classes by frequency of occurrence, have thus far been detected in a sample size of approximately 800 caucasians. Rare Ha-ras alleles, 21 in all, are almost exclusively confined to the genomes of cancer patients (p less than 0.001). From our data we have computed the relative cancer risk associated with possession of a rare Ha-ras allele to be 27. To understand the molecular basis for this phenomenon, we have begun to clone Ha-ras fragments from nontumor DNA of cancer patients. We report here the weak activation, as detected by transfection and transformation of NIH 3T3 mouse cells, of two Ha-ras genes which were obtained from lymphocyte DNA of a melanoma patient. We have mapped the regions that confer this transforming activity to the fragment containing the VTR in one Ha-ras clone and the fragment containing gene coding sequences in the other.
可变串联重复序列（VTR）导致了人c-Ha-ras-1（Ha-ras）基因3'端1千碱基处的高度等位基因现象。在大约800名高加索人的样本中，目前已检测到32个不同的限制性片段，根据出现频率可分为3个等位基因类别。总共21个罕见的Ha-ras等位基因几乎只存在于癌症患者的基因组中（p<0.001）。根据我们的数据，拥有罕见Ha-ras等位基因的相对癌症风险为27。为了理解这一现象的分子基础，我们开始从癌症患者的非肿瘤DNA中克隆Ha-ras片段。我们在此报告，通过转染和转化NIH 3T3小鼠细胞检测到，从一名黑色素瘤患者的淋巴细胞DNA中获得的两个Ha-ras基因具有弱激活作用。我们已经确定，在一个Ha-ras克隆中，赋予这种转化活性的区域位于含有VTR的片段中，而在另一个克隆中，位于含有基因编码序列的片段中。
