BackgroundApproximately 8–15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer.MethodsIn a cross sectional study performed in one reference centre for cancer treatment in São Paulo, Brazil, 100 patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer were included. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA).ResultsNineteen pathogenic mutations (BRCA1: n = 17 and BRCA2: n = 2) featuring 14 different mutations, including two large deletions in BRCA1 (exon 1–2 deleted and exon 5–7 deleted) were identified. Three mutations were detected more than once (c.3331_3334delCAAG, c.5266dupC and c.4484G > T). Two novel frameshift mutations were identified, one in BRCA1 (c.961_962delTG) and one in BRCA2 (c.1963_1963delC). BRCA1/2 mutations were seen in 35.5% of the patients with first and/or second-degree relatives with breast and/or ovarian cancer. Nineteen variants of uncertain significance (VUS) were detected (BRCA1: n = 2 and BRCA2: n = 17), including five distinct missense variants (BRCA1: c.5348 T > C; BRCA2: c.2350A > G, c.3515C > T, c.7534C > T, and c.8351G > A).ConclusionsAmong epithelial ovarian cancer patients unselected for family history of cancer, 19% were BRCA1/2 germline mutation carriers. Almost ¾ of the BRCA mutations, including two large deletions, were detected only once. Our work emphasizes the need of entire gene sequencing and MLPA screening in Brazil.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2966-x) contains supplementary material, which is available to authorized users.

Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation.

Spermatogonial stem cells are responsible for the constant production of spermatozoa. These cells differentiate from the gonocytes, but little is known about these cells and their differentiation into spermatogonia. This study analyzed rat gonocyte proliferation, death and distribution as well as their differentiation into spermatogonia. Rat testes were collected at 19 dpc and at 1, 3, 5, 8, 11 and 15 dpp and submitted to apoptosis investigation through morphological analysis and TUNEL, p53 and cleaved caspase 3 labeling. Ki67 and MVH labeling was used to check gonocyte proliferation and quantification, respectively. OCT4 and DBA labeling were used to check gonocyte differentiation. Seminiferous cord length and gonocyte numerical density were measured to check gonocyte distribution along the seminiferous cords. Although a reduction of gonocyte number per testicular section has been observed from 1 to 5 dpp, the total number of these cells did not change. Apoptotic gonocytes were not detected at these ages, suggesting that the reduction in gonocyte number per testicular section was due to their redistribution along the seminiferous cords, which showed continuous growth from 19 dpc to 5 dpp. The first proliferating germ cells were observed at 8 dpp, coinciding with OCT4 upregulation and with the emergence of the first spermatogonia. In conclusion, this study suggests that (a) gonocytes do not die in the first week after birth, but are rather redistributed along the seminiferous cords just before their differentiation into spermatogonia; (b) mitosis resumption and the emergence of the first spermatogonia are coincident with OCT4 upregulation.