IDENTIFICATION OF FAP LOCUS GENES FROM CHROMOSOME-5Q21
IDENTIFICATION OF FAP LOCUS GENES FROM CHROMOSOME-5Q21
复制标题
DOI：
10.1126/science.1651562
复制
发表时间：
1991-08-09
期刊：
影响因子：
56.9
通讯作者：
NAKAMURA, Y
中科院分区：
文献类型：
--
作者：
KINZLER, KW;NILBERT, MC;NAKAMURA, Y
最近的研究表明，染色体 5q2l 上的一个或多个基因对于结直肠癌的发展非常重要，特别是那些与家族性腺瘤性息肉病 (F") 相关的基因。为了便于识别来自该位点的基因，克隆了与 FAP 紧密连锁的部分区域。分离了包含大约 5.5 Mb DNA 的六个连续序列（重叠群）。来自这些基因座的亚克隆 重叠群用于识别和定位六个基因，所有这些基因都在正常结肠粘膜中表达。其中两个基因（APC 和 MCC）可能与结直肠肿瘤的发生有关。 MCC基因此前已通过其在人类结直肠肿瘤中的突变而被发现。 APC 基因在从 MCC 基因起始的重叠群中被鉴定，并被发现编码异常大的蛋白质。这两人密切 间隔基因编码的蛋白质预计含有卷曲螺旋区域。这两种基因也在多种组织中表达。 MCC 和 APC 及其潜在相互作用的进一步研究应该有助于了解结直肠肿瘤。
Recent studies suggest that one or more genes on chromosome 5q2l are important for the development of colorectal cancers, particularly those associated with familial adenomatous polyposis (F"). To facilitate the identification of genes from this locus, a portion of the region that is tightly linked to FAP was cloned. Six contiguous stretches of sequence (contigs) containing approximately 5.5 Mb of DNA were isolated. Subclones from these contigs were used to identify and position six genes, all of which were expressed in normal colonic mucosa. Two of these genes (APC and MCC) are likely to contribute to colorectal tumorigenesis. The MCC gene had previously been identified by virtue of its mutation in human colorectal tumors. The APC gene was identified in a contig initiated from the MCC gene and was found to encode an unusually large protein. These two closely spaced genes encode proteins predicted to contain coiled-coil regions. Both genes were also expressed in a wide variety of tissues. Further studies of MCC and APC and their potential interaction should prove useful for understanding colorectal neoplasia.