Clinical evaluation of surface treatment on clinical performance of non-carious sclerotic cervical lesions: 18-month follow-up.

PURPOSE: To evaluate the influence of different surface treatments on the clinical behavior of non-carious cervical sclerotic lesions (NCCLs) over an 18-month follow-up period. METHODS: 128 NCCLs from 32 volunteers were randomized into four groups (n=32): G1-control, without preoperative treatment of the dentin surface; G2, dentin conditioning with 17% ethylenediaminetetracetic acid (EDTA) for 2 minutes; G3, increase in dentin surface roughness with diamond bur and G4, increase in dentin surface roughness with diamond bur + dentin conditioning with 17% EDTA for 2 minutes. RESULTS: Differences between groups were tested using the Friedman test (α= 0.05). A questionnaire was administered to volunteers about risk factors related to NCCLs. The relationship between the questionnaire data and the clinical performance of the restorations was analyzed using the multiple logistic regression test (α= 0.05). The variables related to parafunctional habits, anxiety and/or depression were significantly related to the manifestation of postoperative sensitivity. Roughening the sclerotic dentin with a diamond bur increased postoperative sensitivity within 12 months. The presence of parafunctional habits and anxiety/depression may lead to postoperative sensitivity. CLINICAL SIGNIFICANCE: Roughening the sclerotic dentin with a diamond bur increased postoperative sensitivity within 12 months.

Whole-exome sequencing of non-BRCA1/BRCA2 mutation carrier cases at high-risk for hereditary breast/ovarian cancer.

The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer-related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high-risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.

Draft genome of Thermomonospora sp. CIT 1 (Thermomonosporaceae) and in silico evidence of its functional role in filter cake biomass deconstruction.

The filter cake from sugar cane processing is rich in organic matter and nutrients, which favors the proliferation of microorganisms with potential to deconstruct plant biomass. From the metagenomic data of this material, we assembled a draft genome that was phylogenetically related to Thermomonospora curvata DSM 43183, which shows the functional and ecological importance of this bacterium in the filter cake. Thermomonospora is a gram-positive bacterium that produces cellulases in compost, and it can survive temperatures of 60 ºC. We identified a complete set of biomass depolymerizing enzymes in the draft genome of Thermomonospora sp. CIT 1, such as α-amylase, catalase-peroxidases, ß-mannanase, and arabinanase, demonstrating the potential of this bacterium to deconstruct the components of starch, lignin, and hemicellulose. In addition, the draft genome of Thermomonospora sp. CIT 1 contains 18 genes that do not share identity with five other species of Thermomonospora, suggesting that this bacterium has different genetic characteristics than those present in genomes reported so far for this genus. These findings add a new dimension to the current understanding of the functional profile of this microorganism that inhabits agro-industrial waste, which may boost new gene discoveries and be of importance for application in the production of bioethanol.

Draft Genome Sequence of a Chitinophaga Strain Isolated from a Lignocellulose Biomass-Degrading Consortium.

Chitinophaga comprises microorganisms capable of degrading plant-derived carbohydrates, serving as a source of new tools for the characterization and degradation of plant biomass. Here, we report the draft genome assembly of a Chitinophaga strain with 8.2 Mbp and 7,173 open reading frames (ORFs), isolated from a bacterial consortium that is able to degrade lignocellulose.

Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry.

BACKGROUND: There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA. RESULTS: Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian. MATERIALS AND METHODS: This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry. CONCLUSIONS: This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.

Oncogenetics service and the Brazilian public health system: the experience of a reference Cancer Hospital.

The identification of families at-risk for hereditary cancer is extremely important due to the prevention potential in those families. However, the number of Brazilian genetic services providing oncogenetic care is extremely low for the continental dimension of the country and its population. Therefore, at-risk patients do not receive appropriate assistance. This report describes the creation, structure and management of a cancer genetics service in a reference center for cancer prevention and treatment, the Barretos Cancer Hospital (BCH). The Oncogenetics Department (OD) of BCH offers, free of charge, to all patients/relatives with clinical criteria, the possibility to perform i) genetic counseling, ii) preventive examinations and iii) genetic testing with the best quality standards. The OD has a multidisciplinary team and is integrated with all specialties. The genetic counseling process consists (mostly) of two visits. In 2014, 614 individuals (371 families) were seen by the OD. To date, over 800 families were referred by the OD for genetic testing. The support provided by the Oncogenetics team is crucial to identify at-risk individuals and to develop preventive and personalized behaviors for each situation, not only to the upper-middle class population, but also to the people whose only possibility is the public health system.

Association of polymorphisms with a family history of cancer and the presence of germline mutations in the BRCA1/BRCA2 genes.

INTRODUCTION: Breast cancer (BC) is an important public health problem worldwide. In Brazil, breast cancer is the most frequently diagnosed tumor and the leading cause of cancer death in women. Hereditary cancer represents approximately 5 to 10 % of BC cases. Even outside the hereditary cancer context, the presence of polymorphisms acting as genetic modifiers may contribute to a better or worse prognosis. Not much is known about the hereditary BC epidemiology in Brazil or about the influence of polymorphisms on hereditary predisposition. OBJECTIVE: This study examined the role of five different polymorphisms in four groups of women with BC: Group 1: women with a germline mutation in the BRCA1/2 genes; Group 2: women with variants of uncertain significance in BRCA1/2 and Group 3: women with no mutations in BRCA1/2. PATIENTS AND METHODS: The women included in groups 1, 2 and 3 were patients from the Department of Oncogenetics of the Barretos Cancer Hospital who had undergone genetic testing because of a clinical suspicion of hereditary predisposition syndrome. The constitutive DNA was analyzed for the presence of polymorphisms at rs2981582 (FGFR2 gene); rs3803662 (TNRC9); rs889312 (MAP3K1); rs3817198 (LSP1 gene); and rs13281615 (8q24). The analyses were performed using PCR amplification and bi-directional sequencing. RESULTS: No differences were identified in the frequency of the polymorphisms that were analyzed among the three groups. However, some associations were identified, such as the occurrence of bilateral breast cancer and homozygosity for the G allele in rs13281615 as well as the correlation between the SNPs rs2981582 and rs13281615 and the number of cancer cases in the family. Regarding the G allele of rs13281615, we observed that the proportion of individuals who were homozygous for this allele increased with the number of generations affected by cancer, regardless of the group where the patients were included. Concerning the rs2981582 we could observe that individuals from group 1 and homozygous CC had fewer cancer (and also fewer breast cancer) cases. Regarding the hormone receptors, we observed an increased frequency in C homozygotes (rs3803662) among estrogen receptor-negative individuals from groups 1 and 3. For rs2981582 (FGFR2), we observed an increased frequency of the T allele in women who were positive for the estrogen and progesterone receptors regardless of the BRCA1/2 mutational status (p = 0.020 and p = 0.014, respectively). CONCLUSION: The results presented here provide interesting data on the modifying effect of polymorphisms on a family history of cancer; this may be a variable to consider in the analysis of tumor diversity, and of the family history observed in families with hereditary breast cancer (even in those harboring the same type of genetic alteration).

Prevalence of the TP53 p.R337H mutation in breast cancer patients in Brazil.

Germline TP53 mutations predispose individuals to multiple cancers and are associated with Li-Fraumeni/Li-Fraumeni-Like Syndromes (LFS/LFL). The founder mutation TP53 p.R337H is detected in 0.3% of the general population in southern Brazil. This mutation is associated with an increased risk of childhood adrenal cortical carcinoma (ACC) but is also common in Brazilian LFS/LFL families. Breast Cancer (BC) is one of the most common cancers diagnosed in TP53 mutation carriers. We have assessed the prevalence of p.R337H in two groups: (1) 59 BC affected women with a familial history (FH) suggestive of hereditary cancer syndrome but no LFS/LFL features; (2) 815 BC affected women unselected for cancer FH, diagnosed with BC at or before age 45 or at age 55 or older. Among group 1 and group 2 patients, 2/59 (3.4%, CI95%: 0.4%-11.7%) and 70/815 (8.6%, CI95%: 6.8%-10.7%), respectively, were p.R337H carriers in the germline. The prevalence of p.R337H was higher in women diagnosed with BC at or before age 45 (12.1%, CI95%: 9.1%-15.8%) than at age 55 or older (5.1%, CI95%: 3.2%-7.7%), p<0.001). The Brazilian founder p.R337H haplotype was detected in all carriers analysed. These results suggest that inheritance of p.R337H may significantly contribute to the high incidence of BC in Brazil, in addition to its recently demonstrated impact on the risk of childhood ACC.