International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation.

The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156_157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156_157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement.

Hexokinase and phosphofructokinase activity and intracellular distribution correlate with aggressiveness and invasiveness of human breast carcinoma.

Glycolytic enzymes, such as hexokinase and phosphofructokinase, have been reported to be upregulated in many cancer types. Here, we evaluated these two enzymes in 54 breast cancer samples collected from volunteers subjected to mastectomy, and the results were correlated with the prognosis markers commonly used. We found that both enzymes positively correlate with the major markers for invasiveness and aggressiveness. For invasiveness, the enzymes activities increase in parallel to the tumor size. Moreover, we found augmented activities for both enzymes when the samples were extirpated from patients presenting lymph node involvement or occurrence of metastasis. For aggressiveness, we stained the samples for the estrogen and progesterone receptors, HER-2, p53 and Ki-67. The enzyme activities positively correlated with all markers but Ki-67. Finally, we conclude that these enzymes are good markers for breast cancer prognosis.

The R337H mutation in TP53 and breast cancer in Brazil.

BACKGROUND: Germline mutations in p53 are associated with the Li-Fraumeni Syndrome which is characterized by childhood cancers, including pediatric adrenal cortical carcinomas and early onset breast cancer. The high incidence of adrenal cortical carcinomas in southern Brazil is mostly attributed to the R337H mutation in TP53. The relatively high population frequency of this mutation in southern Brazil, along with the clustering of early onset breast cancer in Li-Frameni families, suggests this mutation may also be a low-penetrance breast cancer susceptibility polymorphism. METHODS: We undertook this study to evaluate the frequency of the R337H mutation in breast cancer patients from Rio de Janeiro, Brazil. R337H mutation status was determined in 390 unselected breast cases and 324 controls identified from clinics in Rio de Janeiro, Brazil using a PCR-based assay. RESULTS: Two of the breast cancer cases (0.5%) and none of the controls carried the mutation. Both cases had an early age at diagnosis (< 40 years old) and a family history of breast and other cancers. CONCLUSIONS: These data suggest genetic screening of young onset breast cancer patients should include testing for the R337H mutation.

Prevalence of BRCA1 and BRCA2 mutations in breast cancer patients from Brazil.

The contribution of BRCA1 and BRCA2 to breast cancer incidence in Brazil has not yet been explored. In order to estimate the proportion of breast cancers due to BRCA1 and BRCA2 mutations in Brazil, we conducted a study of unselected breast cancer patients from Rio de Janeiro, Brazil. We enrolled 402 women with breast cancer from a large public hospital and two private medical clinics in the city. A detailed family history was obtained from each patient and a blood sample was obtained for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques, but all mutations were confirmed by direct sequencing. Overall, nine mutations were identified (six in BRCA1 and three in BRCA2) representing 2.3% of the total. The most common mutation, 5382insC in BRCA1, was seen five times and accounted for 56% of all identified mutations. A second mutation, in BRCA2 (6633del5) was seen in two unrelated women. In summary, BRCA1 and BRCA2 mutations are not uncommon in Brazilian women with breast cancer. It appears that a small number of founder mutations may be predominant. Moreover, a small number of founder mutations may be prevalent in Brazil, raising the possibility that a rapid and inexpensive genetic test may be developed to screen for inherited susceptibility to breast cancer in Brazil.

Prevalence of BRCA1 and BRCA2 mutations in breast cancer patients from Brazil

The contribution of BRCA1 and BRCA2 tobreast cancer incidence in Brazil has not yet been explored. In order to estimate the proportion of breast cancers due to BRCA1 and BRCA2 mutations in Brazil,we conducted a study of unselected breast cancer patients from Rio de Janeiro, Brazil. We enrolled 402women with breast cancer from a large public hospital and two private medical clinics in the city. A detailed family history was obtained from each patient and a blood sample was obtained for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques, but all mutations wereconfirmed by direct sequencing. Overall, nine mutations were identified (six in BRCA1 and three in BRCA2)representing 2.3 percent of the total. The most common mutation, 5382insC in BRCA1, was seen five times andaccounted for 56 percent of all identified mutations. A second mutation, in BRCA2 (6633del5) was seen in two unrelatedwomen. In summary, BRCA1 and BRCA2mutations are not uncommon in Brazilian women with breast cancer. It appears that a small number of foundermutations may be predominant. Moreover, a small number of founder mutations may be prevalent inBrazil, raising the possibility that a rapid and inexpensivegenetic test may be developed to screen for inheritedsusceptibility to breast cancer in Brazil.