Futreal P A, Cochran C, Rosenthal J, Miki Y, Swenson J, Hobbs M, Bennett L M, Haugen-Strano A, Marks J, Barrett J C
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
Hum Mol Genet. 1994 Aug;3(8):1359-64. doi: 10.1093/hmg/3.8.1359.
Using the technique of solution hybridization coupled with magnetic bead capture, we have isolated a novel homeobox-containing gene from the BRCA1 region of 17q21. This gene is the human homologue of the mouse Mox1 gene previously localized to a syntenic region of mouse chromosome 11. Multiple overlapping cDNAs of human MOX1 were identified using both a cosmid and a P1 genomic clone containing the microsatellite markers D17S750 and D17S858 which map within the BRCA1 region defined by D17S776 and D17S78. MOX1 expression was observed in a variety of normal tissues examined, including breast and ovary. Given that the gene contains a homeobox domain and has the potential to regulate growth and differentiation, MOX1 represents an attractive candidate for the BRCA1 gene. This possibility was investigated in a series of BRCA1 kindreds and primary sporadic breast tumors. No evidence for mutation was found in the coding sequence, making it unlikely that MOX1 is the BRCA1 gene. However, the widespread expression of MOX1 in non-embryonal tissues suggests a role in normal cell biology which warrants further study.
利用溶液杂交结合磁珠捕获技术，我们从17q21的BRCA1区域分离出一个新的含同源异型框基因。该基因是小鼠Mox1基因的人类同源物，小鼠Mox1基因先前定位于小鼠11号染色体的一个同线区域。使用包含微卫星标记D17S750和D17S858的黏粒和P1基因组克隆鉴定了人类MOX1的多个重叠cDNA，这些微卫星标记位于由D17S776和D17S78定义的BRCA1区域内。在包括乳腺和卵巢在内的多种正常组织中观察到了MOX1的表达。鉴于该基因含有一个同源异型框结构域并具有调节生长和分化的潜力，MOX1是BRCA1基因的一个有吸引力的候选基因。在一系列BRCA1家族和原发性散发性乳腺肿瘤中对这种可能性进行了研究。在编码序列中未发现突变证据，这使得MOX1不太可能是BRCA1基因。然而，MOX1在非胚胎组织中的广泛表达表明其在正常细胞生物学中发挥作用，值得进一步研究。
