Huggins Christopher J, Gill Mona, Andrulis Irene L
Department of Laboratory Medicine, University of Toronto, Ontario, Canada.
Cancer Genet Cytogenet. 2007 Oct 1;178(1):36-41. doi: 10.1016/j.cancergencyto.2007.06.007.
The hLIMD1 gene is located at chromosome 3p21 and was identified as a putative tumor suppressor gene using an elimination test assay. Chromosome 3p21 loci are frequently deleted in a number of cancers, including breast. The 3p21.3 locus harbors a number of tumor suppressor candidates, including LIMD1, a member of the ZYXIN family of genes. LIMD1 directly interacts with RB and is thought to play a role in suppressing tumor growth. To investigate whether mutations in the LIMD1 gene could potentially be involved in breast cancer, we used single-stranded conformation polymorphism analysis on DNA from 235 breast cancers and 95 controls. We identified four novel coding region alterations, including two amino acid substitutions at positions 255 and 302. The two remaining novel variants were found at amino acid positions 246 and 647 and encoded silent alterations. The rare Ser255Arg variant was identified in only sporadic breast tumors (2/165 tumors). Some ZYXIN proteins are phosphorylated by serine/threonine kinases, and the Ser255Arg change is located in a region phosphorylated on serine residues. Together, the data suggest that this variant may warrant further characterization.
hLIMD1基因位于3号染色体p21区域，通过消除试验被鉴定为一个假定的肿瘤抑制基因。3号染色体p21位点在包括乳腺癌在内的多种癌症中经常发生缺失。3p21.3位点包含多个肿瘤抑制候选基因，包括ZYXIN基因家族成员之一的LIMD1。LIMD1直接与RB相互作用，并被认为在抑制肿瘤生长中发挥作用。为了研究LIMD1基因的突变是否可能与乳腺癌有关，我们对235例乳腺癌患者和95例对照的DNA进行了单链构象多态性分析。我们鉴定出四个新的编码区改变，包括255位和302位的两个氨基酸替换。其余两个新变体分别位于246位和647位氨基酸处，编码沉默改变。罕见的Ser255Arg变体仅在散发性乳腺肿瘤中被鉴定出来（165例肿瘤中有2例）。一些ZYXIN蛋白可被丝氨酸/苏氨酸激酶磷酸化，而Ser255Arg改变位于丝氨酸残基磷酸化的区域。总体而言，这些数据表明该变体可能值得进一步研究。
