Ana Osorio

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..It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour...

..To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens...

..These findings may have important consequences for the selection of families with higher probabilities of carrying mutations in the BRCA1 gene...

..However, our results suggest that this variant is absent or very infrequent in our population, making its screening irrelevant from the practical point of view...

..Our results revealed a decrease in p53 apoptotic rate associated with the No Ins-72Pro haplotype...

..We found that combining this relatively easily collected information can be sufficient to classify variants as pathogenic or neutral if tumors from at least three carriers of the same variant can be collected and analyzed...

..Our analysis suggests that RAP80 and CCDC98 do not play an important role as high penetrance breast cancer susceptibility genes...

..In this study, we have evaluated this association in a series of 2932 BRCA1/2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2...

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..In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2...

..This suggests a role for E233G as a low-penetrance susceptibility gene in the specific subgroup of high-risk familial breast cancer cases that are not related to BRCA1/2...

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..Whether later age at first birth is also protective for ovarian cancer in mutation carriers requires further confirmation...

..4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost-effectiveness of genetic testing in familial cancer clinics...

..In addition we have defined a subset of them that have somatic inactivation of the BRCA1 gene...

..We aimed to estimate these penetrances for women attending genetic counseling units in Spain...

..Our results rule out a major role of FANCI, FANCL and FANCM in familial breast cancer susceptibility, suggesting that among the 13 known FA genes, only FANCD1/BRCA2 plays a major role in high-risk breast cancer predisposition...

..CONCLUSION: In summary, our data suggest the existence of two different patterns of evolution, probably common to familial and sporadic breast tumors...

..Further analysis involving a larger set of mutations and different populations are needed to clarify the relevance of this unexpected finding...

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..However, functional prediction analysis and control population studies of both variants ruled out its possible pathogenic role. Our results discard a major contribution of telomere-specific genes in hereditary breast cancer...

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..Therefore, it is of major importance to define the morphological, immunohistochemical, and molecular features of this group of tumors to improve genetic testing and also gain further insight into the biological characteristics of tumors...

..MLPA analysis of positive samples with an alternative set of probes, together with long-range PCR and real-time PCR, is a feasible approach to confirm results in cases in which LGR breakpoints have not been characterized...

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..Our results provide evidence that telomere shortening is associated with earlier age of cancer onset in successive generations, suggesting that it might be a mechanism of genetic anticipation in hereditary breast cancer...

..In this report we propose different approaches to overcome such biases and we present additional data supporting a non-random transmission of BRCA1 mutant alleles...

..This fact suggests that somatic BRCA1 inactivation could modify the profile of tumor progression in most of the BRCAX cases...

..In addition, we provide evidence that KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling...

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..These clinical and functional data indicate a relevant function of HSPC300 in tumor cell progression, and suggest future therapeutic strategies based upon the inhibition of HSPC300 in renal cell carcinoma and possibly on other cancers...

..All the families carrying the 936delAAAC mutation harboured part of a common haplotype shared by other reported carriers, suggesting a possible founder effect for this mutation...

..However, they represent an example showing how different mutations of the same gene may be associated with specific histological subtypes of cancer...

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..Our results are in agreement with the idea that a great proportion of moderate-risk cancer families could be due to low penetrance susceptibility genes distinct from BRCA1 or BRCA2...

..Mutation screening of the MEN1 gene using CSGE was demonstrated to be a fast, simple, and inexpensive method to study patients suspected of having MEN1 disease...

..3%), including two with male breast cancer. Three of the mutations were frameshift and one was a missense. Two of the mutations have been previously published and two are new mutations...

..Here, we describe molecular signatures that define BRCA1 subclasses depending on the expression of the gene encoding for oestrogen receptor, ESR1...

..Our data are similar to those obtained in SBC studies, highlighting the existence of distinct genetic pathways of tumor evolution, common to both SBC and FBC...

..Our results suggest that these six mutations are not specially recurrent in the Spanish population and that differences in the geographical origin of the families can influence the type and proportion of mutations identified...

..Most important, the critical region of AI coincides with a female hot spot of recombination, suggesting a possible correlation between the two regions...

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..1 cM. Our results suggest that these families shared a common ancestry with BRCA2 9254del5, which is a founder mutation originating in the Northeast Spanish, with an estimated age of 92 (95% CI 56-141) generations...

..Thus, 135G-->C may modify the risk of breast cancer in BRCA2 mutation carriers by altering the expression of RAD51. RAD51 is the first gene to be reliably identified as a modifier of risk among BRCA1/2 mutation carriers...

..Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown...

..Knowledge of the spectrum of mutations and their geographical distribution in Spain will allow a more effective detection strategy in countries with large Spanish populations...

..We aimed to establish if BRCA1/BRCA2 mutation carriers could be distinguished from noncarriers based on expression profiling of normal cells...

..CONCLUSION: Our results suggest that BRCA2 tumors demonstrate more cytoplasmic and less nuclear RAD51 staining, and increased CHEK2 staining. This pattern may distinguish BRCA2 from familial non-BRCA1/2 tumors...

..65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer...