Strazisar Mojca, Mlakar Vid, Glavac Damjan
Department of Molecular Genetics, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
Lung Cancer. 2009 Jun;64(3):257-62. doi: 10.1016/j.lungcan.2008.09.011. Epub 2008 Nov 12.
LATS2 is a new member of the LATS tumour suppressor family. The human LATS2 gene is located at chromosome 13q11-12, a hot spot (67%) for loss of heterozygosity (LOH) in non-small cell lung cancer (NSCLC). We screened 129 non-small cell lung cancer samples and 13 lung cancer cell lines, initially for mutations in the LATS2 gene and subsequently for mutations in P53 and K-RAS genes. Either polymorphisms or mutations were identified in over 50 percent of analysed tumours. A novel missense mutation, S1073R, and a large deletion of 8 amino acids in the PAPA-repeat region were detected in 9 and 2 NSCLC tumours, respectively. Those mutations were not identified in the 13 lung cancer cell lines. Mutations were tumour specific and were absent from adjacent normal tissue and healthy controls. Down-regulation of the LATS2 gene was observed in most NSCLC tumours but was not related to any mutation or polymorphism. Tumours with a LATS2 mutation often also harbour a P53 but not K-RAS gene mutation and were mostly in an advanced stage of development, with regional lymph node involvement.
LATS2是LATS肿瘤抑制家族的新成员。人类LATS2基因位于染色体13q11 - 12，这是非小细胞肺癌（NSCLC）中杂合性缺失（LOH）的热点区域（67%）。我们筛查了129份非小细胞肺癌样本和13个肺癌细胞系，首先检测LATS2基因的突变，随后检测P53和K - RAS基因的突变。在超过50%的分析肿瘤中鉴定出多态性或突变。分别在9例和2例非小细胞肺癌肿瘤中检测到一种新的错义突变S1073R和PAPA重复区域8个氨基酸的大片段缺失。在13个肺癌细胞系中未发现这些突变。突变具有肿瘤特异性，在相邻正常组织和健康对照中不存在。在大多数非小细胞肺癌肿瘤中观察到LATS2基因下调，但与任何突变或多态性无关。具有LATS2突变的肿瘤通常也伴有P53基因突变而非K - RAS基因突变，且大多处于晚期，伴有区域淋巴结受累。
