Genetic expression profiles and chromosomal alterations in sporadic breast cancer in Mexican women.

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.

FMR1 CGG repeat distribution and linked microsatellite-SNP haplotypes in normal Mexican Mestizo and indigenous populations.

The (CGG)n repeat size distribution in the FMR1 gene was studied in healthy individuals: 80 X chromosomes of Mexican Mestizos from Mexico City and 33 X chromosomes of Mexican Amerindians from three indigenous communities (Purepechas, Nahuas, and Tzeltales), along with alleles and haplotypes defined by two microsatellite polymorphic markers (DXS548 and FRAXAC1) and two single nucleotide polymorphisms (FMRA and FMRB). Genetic frequencies of Mestizo and Amerindian subpopulations were statistically similar in almost all cases and thus were considered one population for comparisons with other populations. Sixteen (CGG)n alleles in the 17-38 size range were observed, and the most common were the 25 (38.0%), 26 (28.3%), and 24 (12.3%) repeat alleles. This pattern differs from most other populations reported, but a closer relation to Amerindian, European, and African populations was found, as expected from the historical admixture that gave rise to Mexican Mestizos. The results of the CA repeats analysis at DXS548-FRAXAC1 were restricted to nine haplotypes, of which haplotypes 7-4 (52.2%), 8-4 (23.8%), and 7-3 (11.5%) were predominant. The modal haplotype 7-4, instead of the nearly universal haplotype 7-3, had been reported exclusively in Eastern Asian populations. Likewise, only seven different FRAXAC1-FMRA-FMRB haplotypes were observed, including five novel haplotypes (3TA, 4TA, 3 - A, 4 - A, and 5 - A), compared with Caucasians. Of these, haplotypes - A (78.7%) and 3 - A (13.2%) were the most common in the Mexican population. These data suggest a singular but relatively low genetic diversity at FMR1 in the studied Mexican populations that may be related to the recent origin of Mestizos and the low admixture rate of Amerindians.

Polymorphism distribution of Int13, Int22, and St14 VNTRs in a Mexican population and their application in carrier diagnosis of hemophilia A.

Variable nucleotide tandem repeats (VNTR) Int13, Int22, and St14 were analyzed to determine polymorphic distribution in normal individuals from Mexico's central region and their efficacy in detecting hemophilia A carriers. Polymerase chain reaction (PCR) was carried out on 166 X chromosomes from unrelated Mexicans, and the same method was applied to detect carriers in hemophilia A families. Screening revealed the existence of at least eight different alleles for Int13, 4 alleles for Int22, and 10 alleles for St14. Their heterozygosity rates were 41.3%, 52.6%, and 83%, respectively. Compared to Caucasians, the Mexican population showed a markedly low heterozygosity rate for the Int13 marker. However, Int22 showed a heterozygosity that was similar to Turkish and Chinese populations. The St14 marker was the most informative in carrier diagnosis, and a new 680-bp allele not previously reported was detected. Carrier diagnosis was performed in 39 women from eight different hemophilia A families. Fifteen (38%) females were not carriers, 16 (41%) females were carriers, and 8 (21%) were homozygous. Determination of polymorphisms in VNTR markers revealed that St14 was the most useful for hemophilia A carrier detection in Mexico.