Valladares Adán, Hernández Normand García, Gómez Fabio Salamanca, Curiel-Quezada Everardo, Madrigal-Bujaidar Eduardo, Vergara Ma Dolores, Martínez Mónica Sierra, Arenas Aranda Diego J
Molecular Genetics Laboratory, Medical Research Unit, Pediatric Hospital, Centro Médico Nacional Siglo XXI (CMN-SXXI), Instituto Mexicano del Seguro Social (IMMS), Col Doctores, CP 06720, Del Cuauhtémoc, Mexico City, Mexico.
Cancer Genet Cytogenet. 2006 Oct 15;170(2):147-51. doi: 10.1016/j.cancergencyto.2006.06.002.
Breast cancer is the second-leading cause of death among Mexican women >35 years of age. At the molecular level, changes in many genetic pathways have been reported to be associated with this neoplasm. To analyze these changes, we determined gene expression profiles and chromosomal structural alterations in tumors from Mexican women. We obtained mRNA to identify expression profiles with microarray technology, and DNA to determine amplifications and deletions, in 10 fresh sporadic breast tumor biopsies without treatment, as well as in 10 nonaffected breast tissues. Expression profiles were compared with genetic changes observed by comparative genomic hybridization (CGH). We compared the expression profiles against the structural alterations from the studied genes by means of microarrays; at least 17 of these genes correlated with DNA copy number alterations. We found that the following genes were overexpressed: LAMC1, PCTK3, CCNC, CCND1, FGF3, PCTK2, L1CAM, BGN, and PLXNB3 (alias PLEXR). Underexpressed genes included CASP9, FGR, TP73, HSPG2, and ERCC1; genes turned off included FRAP1, EPHA2 (previously ECK), IL12A, E2F5, TNFRSF10B, TNFRSF10A, EFNB3, and BCL2. The results will allow us, in the near future, to outline genes that could serve as diagnostic, prognostic, or target therapy markers for the Mexican population.
乳腺癌是墨西哥35岁以上女性的第二大死因。在分子水平上,据报道许多基因通路的变化与这种肿瘤有关。为了分析这些变化,我们测定了墨西哥女性肿瘤中的基因表达谱和染色体结构改变。我们从10例未经治疗的新鲜散发性乳腺肿瘤活检组织以及10例未受影响的乳腺组织中获取mRNA以通过微阵列技术鉴定表达谱,并获取DNA以确定扩增和缺失情况。将表达谱与通过比较基因组杂交(CGH)观察到的基因变化进行比较。我们通过微阵列将表达谱与所研究基因的结构改变进行比较;其中至少17个基因与DNA拷贝数改变相关。我们发现以下基因过表达:LAMC1、PCTK3、CCNC、CCND1、FGF3、PCTK2、L1CAM、BGN和PLXNB3(别名PLEXR)。低表达基因包括CASP9、FGR、TP73、HSPG2和ERCC1;关闭的基因包括FRAP1、EPHA2(以前称为ECK)、IL12A、E2F5、TNFRSF10B、TNFRSF10A、EFNB3和BCL2。这些结果将使我们在不久的将来能够勾勒出可作为墨西哥人群诊断、预后或靶向治疗标志物的基因。