Gene expression profiling identifies WNT7A as a possible candidate gene for decreased cancer risk in fragile X syndrome patients.
OBJECTIVE
Although sporadic cases of cancer in patients with fragile X syndrome (FXS) have been reported, extensive studies carried out in Denmark and Finland concluded that cancer incidence in these patients is lower than in the general population. On the other hand, the FMR1 protein, which is involved in the translation process, is absent in FXS patients. Hence, it is reasonable to assume that these patients exhibit an abnormal expression of some proteins involved in regulating tumor suppressor genes and/or oncogenes, thus explaining its decreased cancer frequency. We undertook this study to analyze the expression of oncogenes and tumor suppressor genes in fragile X syndrome patients.


METHODS
Molecular analysis of the FMR1 gene was achieved in 10 male patients and controls. Total RNA from peripheral blood was used to evaluate expression of oncogenes and tumor suppressor genes included in a 10,000 gene microarray library. Quantitative real-time PCR was utilized to confirm genes with differential expression.


RESULTS
Among 27 genes showing increased expression in FXS patients, only eight genes exhibited upregulation in at least 50% of them. Among these, ARMCX2 and PPP2R5C genes are tumor suppressor related. Likewise, 23/65 genes showed decreased expression in >50% of patients. Among them, WNT7A gene is a ligand of the beta-catenin pathway, which is widely related to oncogenic processes. Decreased expression of WNT7A was confirmed by quantitative RT-PCR. Expression of c-Myc, c-Jun, cyclin-D and PPARdelta genes, as target of the beta-catenin pathway, was moderately reduced in FXS patients.


CONCLUSIONS
Results suggest that this diminished expression of the WNT7A gene may be related to a supposed protection of FXS patients to develop cancer.
Rosales-Reynoso
Mónica Alejandra
MA
División de Medicina Molecular, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México. pbarros_gdl@yahoo.com.mx
Ochoa-Hernández
Alejandra Berenice
AB
Aguilar-Lemarroy
Adriana
A
Jave-Suárez
Luis Felipe
LF
Troyo-Sanromán
Rogelio
R
Barros-Núñez
Patricio
P
D005600:Fragile X Syndrome / Q000150:complications* / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D051153:Wnt Proteins / Q000235:genetics*
C092778:WNT7A protein, human; D051153:Wnt Proteins