We report on the screening of the entire BRCA1/BRCA2 coding sequence by SSCP, PTT, and direct sequencing in 68 Italian families with recurrent breast or ovarian cancer. For each investigated proband, the probability of being carrier of a BRCA1/BRCA2 mutation was evaluated using the BRCAPRO software. We detected BRCA1/BRCA2 mutations in 8 patients (11.7%). However, if considering only patients with a carrier probability >10%, the detection rate was 36.8%, confirming the usefulness of the BRCAPRO software. One change (BRCA1 4172insT) was a novel mutation not reported in BIC database.

Background: No data have been so far reported on the relationship between polymorphisms of LEP gene and cardiovascular disease. Patients and methods: We genotyped a tetranucleotide repeat mapped in the 3 0 UTR of the LEP gene (LEP-tet) in 109 subjects with cardiovascular events and in 109 control subjects. Results: Univariate analysis and multivariate logistic regression analysis adjusted for age, gender, smoking status, history of hyperlipidemia, hypertension or diabetes showed not significant association between the genotype of the LEP-tet and cardiovascular diseases. Moreover, no differences were observed in the plasma leptin concentrations between cases and control subjects (22719 vs 22714 ng/ml, P ¼ 0.52) and in relation to the LEP-tet classes or carriage of specific allelels (P ¼ 0.76 for the association between LEP-tet classes and leptin levels in overall analysis). Conclusions: In conclusion, our data do not support an association between the LEP-tet microsatellite polymorphism of the human LEP gene and cardiovascular diseases.

Twenty-two Sardinian families with multiple cases of hypercholesterolemia were investigated with six polymorphic markers of the low-density lipoprotein receptor (LDLR) gene that could be quickly analyzed by PCR-based methods. Five single nucleotide polymorphisms (SNP) in exons 8, 10, 13, 15, and 18 and a microsatellite marker flanking the 3' end of the LDLR gene were used to define the haplotypes at the LDLR locus for familial hypercholesterolemia (FH) diagnosis within families. No significant differences were observed between the allele frequencies of the normal and mutant chromosomes. In two families, hypercholesterolemia did not cosegregate with the LDLR locus. In the remaining 20 FH chromosomes, seven different haplotypes were identified. The same haplotypes were found with a similar frequency among the 61 normal chromosomes. Other five haplotypes were characteristic only of normal chromosomes. These data provide no evidence for a gene founder effect in the Sardinian population and, instead, highlight a pattern of genetic heterogeneity comparable with that found in mainland European populations. The replacement of the restriction fragment length polymorphisms currently used in the genetic analysis of FH with PCR-based markers proved to be a simple and less time-consuming method and did not reduce informativity in the molecular analysis of FH families.

Basal-like breast cancer (BBC) and Glioblastoma Multiforme (GBM) are aggressive cancers associated with poor prognosis. BBC and GBM express stem gene expression signatures which are in part driven by FOXO transcription factors. To gain further insight into the impact of FOXO1 in BBC, we treated BT549 cells with the FOXO1 inhibitor AS1842856 and performed RNA Seq. Gene Set Enrichment Analysis (GSEA) with RNA Seq. data indicated that a set of WNT target genes including LEF1 and AXIN2 were robustly induced after 48-hours of AS1842856 treatment. These same genes were also induced in GBM cell lines U87MG, LN18, LN229, A172, and DBTRG upon AS1842856 treatment. RNAi targeting of FOXO1 led to reduced LEF1 gene expression in BT549 and U87MG cells at 18-hour and 24-hour timepoints respectively. CRISPR Cas9-mediated FOXO1 disruption led to reduced expression of canonical WNT target gene LEF1 in U87MG cells. Citation Format: Megan Keniry, Shania Pintor, Alma Lopez, David Flores. FOXO transcription factors regulate WNT pathway gene expression in GBM [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1475.

Twenty‐two Sardinian families with multiple cases of hypercholesterolemia were investigated with six polymorphic markers of the low‐density lipoprotein receptor (LDLR) gene that could be quickly analyzed by PCR‐based methods. Five single nucleotide polymorphisms (SNP) in exons 8, 10, 13, 15, and 18 and a microsatellite marker flanking the 3′ end of the LDLR gene were used to define the haplotypes at the LDLR locus for familial hypercholesterolemia (FH) diagnosis within families. No significant differences were observed between the allele frequencies of the normal and mutant chromosomes. In two families, hypercholesterolemia did not cosegregate with the LDLR locus. In the remaining 20 FH chromosomes, seven different haplotypes were identified. The same haplotypes were found with a similar frequency among the 61 normal chromosomes. Other five haplotypes were characteristic only of normal chromosomes. These data provide no evidence for a gene founder effect in the Sardinian population and, instead, highlight a pattern of genetic heterogeneity comparable with that found in mainland European populations. The replacement of the restriction fragment length polymorphisms currently used in the genetic analysis of FH with PCR‐based markers proved to be a simple and less time‐consuming method and did not reduce informativity in the molecular analysis of FH families. Am. J. Med. Genet. 91:34–38, 2000. © 2000 Wiley‐Liss, Inc.