Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA). RESULTS: Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. CONCLUSIONS: From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

Genomic Analyses of Germline and Somatic Variation in High-Grade Serous Ovarian Cancer.

Background High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 577 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations. Results Approximately one-third of tumors had loss-of-function germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM , and PALB2 . Loss-of-function germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP , and NF1 . In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of loss-of-function variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536 , and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. Conclusions From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 577 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

Abundance and population structure of Plesionika narval (Fabricius, 1787) in the Northeastern Atlantic / Abundância e estrutura populacional de Plesionika narval (Fabricius, 1787) no Atlântico Nordeste

Abstract Analysis of abundance and population structure of Plesionika narval was performed on data concerning 5,255 specimens obtained from 62 fishing sets carried out off the Madeira archipelago (Northeastern Atlantic) between 2004 and 2008 in a depth range from 101 to 350 m. Abundance ranged from 0.01 to 19.74 specimens-per-trap and significant differences were found between seasons, probably as a result of an increment of population in the spring during the recruitment season. The analysis of size distribution revealed that the carapace length (CL) ranged from 2.45 to 28.61 mm and that mean female size consistently exceeded that of males. Differences in mean CL were statistically significant between depth strata and seasons. Of the specimens sampled, 57.00% were males, 41.88% females and 1.42% undetermined. Sex ratio also differed significantly between seasons according to depth strata, consolidating the hypothesis of the existence of seasonal migrations related with the reproductive cycle of this species. Ovigerous females showed larger sizes and occurred all year around and remain in shallow waters in winter, summer and autumn and move to deeper waters in spring. The highest frequency of ovigerous females was recorded in summer, between 151 and 200 m deep supporting the hypothesis that spawning of this species occurs in shallow waters, especially in late summer.

Resumo O estudo de abundância e dinâmica populacional de Plesionika narval foi efetuado com 5.255 espécimes provenientes de 62 lances de pesca realizados ao largo do arquipélago da Madeira (Atlântico Nordeste) de 2004 a 2008 entre 101 e 350 m de profundidade. A abundância oscilou entre 0,01 e 19,74 espécimes-por-armadilha com diferenças significativas entre estações provavelmente devido ao aumento da população na primavera durante o período de recrutamento. A análise da distribuição de tamanhos revelou que o comprimento da carapaça (CL) variou entre 2,45 e 28,61 mm e que o tamanho médio das fêmeas excedeu o dos machos. Verificaram-se diferenças significativas no CL médio entre estrato de profundidade e estação. Do total amostrado, 57,00% foram machos, 41,88% fêmeas e 1,42% indeterminados. A razão de sexos também diferiu significativamente entre estações de acordo com a profundidade, consolidando a hipótese da existência de migrações sazonais relacionadas com o ciclo reprodutivo desta espécie. As fêmeas ovadas apresentaram maiores tamanhos e ocorreram durante todo o ano permanecendo em águas pouco profundas no inverno, verão e outono e migrando para águas profundas na primavera. A maior frequência de fêmeas ovadas foi registada no verão, entre 151 e 200 m de profundidade reforçando a hipótese de que a desova desta espécie ocorre em águas menos profundas, especialmente no final do verão.

Abundance and population structure of Plesionika narval (Fabricius, 1787) in the Northeastern Atlantic.

Analysis of abundance and population structure of Plesionika narval was performed on data concerning 5,255 specimens obtained from 62 fishing sets carried out off the Madeira archipelago (Northeastern Atlantic) between 2004 and 2008 in a depth range from 101 to 350 m. Abundance ranged from 0.01 to 19.74 specimens-per-trap and significant differences were found between seasons, probably as a result of an increment of population in the spring during the recruitment season. The analysis of size distribution revealed that the carapace length (CL) ranged from 2.45 to 28.61 mm and that mean female size consistently exceeded that of males. Differences in mean CL were statistically significant between depth strata and seasons. Of the specimens sampled, 57.00% were males, 41.88% females and 1.42% undetermined. Sex ratio also differed significantly between seasons according to depth strata, consolidating the hypothesis of the existence of seasonal migrations related with the reproductive cycle of this species. Ovigerous females showed larger sizes and occurred all year around and remain in shallow waters in winter, summer and autumn and move to deeper waters in spring. The highest frequency of ovigerous females was recorded in summer, between 151 and 200 m deep supporting the hypothesis that spawning of this species occurs in shallow waters, especially in late summer.

Prospective study of the fishery of the shrimp Plesionika narval (Fabricius, 1787) in the Northeastern Atlantic / Estudo prospectivo da pesca do camarão Plesionika narval (Fabricius, 1787) no Atlântico Nordeste

Abstract Several experimental surveys were carried out in the Northeastern Atlantic, Madeira archipelago from 1991 to 2008 to explore new fisheries resources. This study examined the selectivity of bottom and floating traps and the analysis of yield-per-recruit (YPR) and biomass-per-recruit (BPR) providing helpful insight to the management of the shrimp Plesionika narval. A total of 28,262 specimens were sampled and the analysis of length at first capture returned higher values when using floating traps indicating that these traps are more selective, exerting less pressure on the resource. The YPR and BPR analysis showed that the stock is under exploited for the studied area and suggests that the use of floating traps in the commercial fisheries of P. narval is recommended, which will allow a higher maximum allowable limit of exploitation and greater yield. The results suggest that P. narval has the potential to support a viable and sustainable fishery using floating traps.

Resumo Vários cruzeiros de investigação foram realizados no Atlântico Nordeste, arquipélago da Madeira entre 1991 e 2008 visando a exploração de novos recursos pesqueiros. O presente estudo contemplou a comparação da seletividade de pesca entre armadilhas de fundo e flutuantes e a análise de rendimento por recruta (YPR) e biomassa por recruta (BPR) facultando informação essencial para a gestão do camarão Plesionika narval. Um total de 28,262 especimens foram amostrados e a análise de comprimento de primeira captura retornou valores mais elevados aquando da utilização de armadilhas flutuantes, indicando que essas armadilhas são mais seletivas e exercem menos pressão sobre o recurso. A análise YPR e BPR mostrou que o estoque se encontra sob explorado para a área de estudo e recomenda a utilização de armadilhas flutuantes na pesca comercial de P. narval, que permitirão um limite máximo de exploração com rendimento superior. Os resultados sugerem que P. narval tem o potencial para suportar uma pescaria viável e sustentável mediante a utilização de armadilhas flutuantes.

Prospective study of the fishery of the shrimp Plesionika narval (Fabricius, 1787) in the Northeastern Atlantic

Abstract Several experimental surveys were carried out in the Northeastern Atlantic, Madeira archipelago from 1991 to 2008 to explore new fisheries resources. This study examined the selectivity of bottom and floating traps and the analysis of yield-per-recruit (YPR) and biomass-per-recruit (BPR) providing helpful insight to the management of the shrimp Plesionika narval. A total of 28,262 specimens were sampled and the analysis of length at first capture returned higher values when using floating traps indicating that these traps are more selective, exerting less pressure on the resource. The YPR and BPR analysis showed that the stock is under exploited for the studied area and suggests that the use of floating traps in the commercial fisheries of P. narval is recommended, which will allow a higher maximum allowable limit of exploitation and greater yield. The results suggest that P. narval has the potential to support a viable and sustainable fishery using floating traps.

Resumo Vários cruzeiros de investigação foram realizados no Atlântico Nordeste, arquipélago da Madeira entre 1991 e 2008 visando a exploração de novos recursos pesqueiros. O presente estudo contemplou a comparação da seletividade de pesca entre armadilhas de fundo e flutuantes e a análise de rendimento por recruta (YPR) e biomassa por recruta (BPR) facultando informação essencial para a gestão do camarão Plesionika narval. Um total de 28,262 especimens foram amostrados e a análise de comprimento de primeira captura retornou valores mais elevados aquando da utilização de armadilhas flutuantes, indicando que essas armadilhas são mais seletivas e exercem menos pressão sobre o recurso. A análise YPR e BPR mostrou que o estoque se encontra sob explorado para a área de estudo e recomenda a utilização de armadilhas flutuantes na pesca comercial de P. narval, que permitirão um limite máximo de exploração com rendimento superior. Os resultados sugerem que P. narval tem o potencial para suportar uma pescaria viável e sustentável mediante a utilização de armadilhas flutuantes.

Prospective study of the fishery of the shrimp Plesionika narval (Fabricius, 1787) in the Northeastern Atlantic.

Several experimental surveys were carried out in the Northeastern Atlantic, Madeira archipelago from 1991 to 2008 to explore new fisheries resources. This study examined the selectivity of bottom and floating traps and the analysis of yield-per-recruit (YPR) and biomass-per-recruit (BPR) providing helpful insight to the management of the shrimp Plesionika narval. A total of 28,262 specimens were sampled and the analysis of length at first capture returned higher values when using floating traps indicating that these traps are more selective, exerting less pressure on the resource. The YPR and BPR analysis showed that the stock is under exploited for the studied area and suggests that the use of floating traps in the commercial fisheries of P. narval is recommended, which will allow a higher maximum allowable limit of exploitation and greater yield. The results suggest that P. narval has the potential to support a viable and sustainable fishery using floating traps.

Abundance and population structure of Plesionika narval (Fabricius, 1787) in the Northeastern Atlantic

Abstract Analysis of abundance and population structure of Plesionika narval was performed on data concerning 5,255 specimens obtained from 62 fishing sets carried out off the Madeira archipelago (Northeastern Atlantic) between 2004 and 2008 in a depth range from 101 to 350 m. Abundance ranged from 0.01 to 19.74 specimens-per-trap and significant differences were found between seasons, probably as a result of an increment of population in the spring during the recruitment season. The analysis of size distribution revealed that the carapace length (CL) ranged from 2.45 to 28.61 mm and that mean female size consistently exceeded that of males. Differences in mean CL were statistically significant between depth strata and seasons. Of the specimens sampled, 57.00% were males, 41.88% females and 1.42% undetermined. Sex ratio also differed significantly between seasons according to depth strata, consolidating the hypothesis of the existence of seasonal migrations related with the reproductive cycle of this species. Ovigerous females showed larger sizes and occurred all year around and remain in shallow waters in winter, summer and autumn and move to deeper waters in spring. The highest frequency of ovigerous females was recorded in summer, between 151 and 200 m deep supporting the hypothesis that spawning of this species occurs in shallow waters, especially in late summer.

Resumo O estudo de abundância e dinâmica populacional de Plesionika narval foi efetuado com 5.255 espécimes provenientes de 62 lances de pesca realizados ao largo do arquipélago da Madeira (Atlântico Nordeste) de 2004 a 2008 entre 101 e 350 m de profundidade. A abundância oscilou entre 0,01 e 19,74 espécimes-por-armadilha com diferenças significativas entre estações provavelmente devido ao aumento da população na primavera durante o período de recrutamento. A análise da distribuição de tamanhos revelou que o comprimento da carapaça (CL) variou entre 2,45 e 28,61 mm e que o tamanho médio das fêmeas excedeu o dos machos. Verificaram-se diferenças significativas no CL médio entre estrato de profundidade e estação. Do total amostrado, 57,00% foram machos, 41,88% fêmeas e 1,42% indeterminados. A razão de sexos também diferiu significativamente entre estações de acordo com a profundidade, consolidando a hipótese da existência de migrações sazonais relacionadas com o ciclo reprodutivo desta espécie. As fêmeas ovadas apresentaram maiores tamanhos e ocorreram durante todo o ano permanecendo em águas pouco profundas no inverno, verão e outono e migrando para águas profundas na primavera. A maior frequência de fêmeas ovadas foi registada no verão, entre 151 e 200 m de profundidade reforçando a hipótese de que a desova desta espécie ocorre em águas menos profundas, especialmente no final do verão.

Gill monogeneans of the chub mackerel, Scomber japonicus from Madeiran waters of the Atlantic Ocean, Portugal.

Five species of monogeneans were recovered from the gill filaments of 181 chub mackerel, Scomber japonicus, from the Madeiran waters of the Atlantic Ocean, Portugal, during 2004/2005. The monogenean Pseudokuhnia minor showed the highest prevalence (98.68%) and a mean intensity of 28.23, followed by Kuhnia scombri (prevalence of 43.71% and mean intensity of 2.69) and K. scombercolias (prevalence of 39.1% and a mean intensity of 1.81). Kuhnia sprostonae and Grubea cochlear were rare, occurring in only one and five fish hosts respectively. No correlation between fish host length and mean intensity of infection with the three most abundant monogeneans was found. However, significant differences in prevalence and abundance were found in relation to date of sampling for P. minor, and all parasites were aggregated in their distribution.

Reliability assessment of soluble c-erbB-2 concentrations in the saliva of healthy women and men.

BACKGROUND: The protein c-erb B-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsy specimens from women diagnosed with malignant tumors. Current studies suggest that soluble fragments of the c-erb B-2 oncogene may be released from the cell surface and become detectable in patients with a carcinoma of the breast. Consequently, the purpose of this study is to assay soluble c-erb B-2 protein in the saliva of healthy men and women to determine the reliability of the assay. METHODS: To determine the diagnostic utility of this oncogene, we assayed the soluble form of the c-erb B-2 protein in the saliva with an enzyme-linked immunosorbent assay. The study population consisted of 10 healthy women and 9 healthy men who were serially sampled for saliva 3 times a day for a 5-day period. Saliva was collected from each subject at 9 AM, 4 PM, and 9 PM during the 5-day period. RESULTS: We found the presence of c-erb B-2 protein in the saliva of both groups of subjects. The salivary levels of c-erb B-2 were not significantly different when compared for gender differences. Likewise, the results suggest that sampling during various times of the day for salivary c-erb B-2 levels has no effect on marker concentration. Reliability analyses showed that supervised salivary collections were more reliable than unsupervised collections. CONCLUSIONS: The results of this pilot study suggest that the assay for salivary c-erb B-2 protein is reliable and might have potential use in the initial detection and follow-up screening for the recurrence of breast cancer in both men and women.

Myxoid angiomyoma of the hard palate: a case report.

Angiomyomas are found with some frequency in the female genital tract. They can also appear in both sexes in the gastrointestinal tract and in the skin. The oral cavity is an unusual site for an angiomyoma. In this article, we describe the case of a 74-year-old woman who came to us with a nodule at the palatal midline. Following surgical excision of the growth and stent placement over the wound site, a biopsy analysis was performed. Histology of the removed tissue revealed an unusual variant of an angiomyoma: a myxoid angiomyoma.

The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study.

The protein c-erbB-2, also known as Her2/neu, is a prognostic breast cancer marker assayed in tissue biopsies from women diagnosed with malignant tumors. Present studies suggest that soluble fragments of the c-erbB-2 oncogene may be released from the cell surface and become detectable in patients with carcinoma of the breast. Consequently, the purpose of this study was to assay the c-erbB-2 protein in the saliva and serum of women with and without carcinoma of the breast and to determine whether the protein possesses any diagnostic value. To determine the diagnostic utility of this oncogene, the soluble form of the c-erbB-2 protein was assayed in the saliva and serum using ELISA in three different groups of women. The three groups consisted of 57 healthy women, 41 women with benign breast lesions, and 30 women diagnosed with breast cancer. To compare the relative diagnostic utility of the c-erbB-2 protein, CA 15-3 was also measured. The CA 15-3 measurements served as a "gold standard" by which to compare the c-erbB-2 protein's diagnostic effectiveness. We found c-erbB-2 protein in the saliva and serum of all three groups of women. The salivary and serological levels of c-erbB-2 in the cancer patients, however, were significantly higher (P < 0.001) than the salivary and serum levels of healthy controls and benign tumor patients. Additionally, the c-erbB-2 protein was found to be equal to or to surpass the ability of CA 15-3 to detect patients with carcinoma. The results of the pilot study suggest that the c-erbB-2 protein may have potential use in the initial detection and/or follow-up screening for the recurrence of breast cancer in women.

Oral contraceptive usage and the expression of CA 15-3 and c-erbB-2 in the saliva of healthy women.

OBJECTIVE: This study was conducted to determine if oral contraceptive use affected the salivary levels of 2 cancer biomarkers, cancer antigen 15-3 (CA 15-3), and c-erbB-2 (erb) among women. STUDY DESIGN: A total of 40 women were recruited for this study, 20 controls and 20 using oral contraceptives. The average ages were 27.4 years (control) and 27.1 years (using estrogen supplements). Stimulated whole saliva specimens were collected from each woman. CA 15-3 levels were determined using enzyme immunoassay (EIA) while c-erbB-2 levels were determined by standard ELISA methods. RESULTS: Findings from this study indicate that there were no significant differences between the control and study groups. CONCLUSIONS: Therefore, saliva may be a useful tool for monitoring women with high estrogen levels due to either tumor load or any treatment regimen, i.e., the levels of the cancer biomarkers CA 15-3 and erb are not affected by increased levels of estrogen in the body.

CA 15-3 and c-erbB-2 presence in the saliva of women.

Two markers used to aid in the diagnosis and treatment of breast cancer were examined in the saliva of a cohort of 135 healthy women. The investigators detected the presence of cancer antigen 15-3 (CA 15-3) and c-erbB-2 in the saliva sampled from the 135 women. The marker concentrations for CA 15-3 and c-erbB-2 were also evaluated and compared in terms of tobacco usage, menopausal status, estrogen usage, systemic diseases, prescription medications, race, and age. The results of the study showed no association between the aforementioned variables and salivary marker concentrations. The results of this study establish a baseline for measuring the biomarkers in the saliva of women with no evidence of malignant disease and add further support to the notion that salivary concentrations of CA 15-3 and c-erbB-2 may be useful in the detection of breast cancer and/or the post operative follow-up of patients being treated for carcinoma of the breast.

Alternative treatments for a traumatic bone cyst: a longitudinal case report.

A patient presented with a large, multilocular, refractory traumatic bone cyst. The radiolucency had increased in dimension since her last recall. Over 11 years, therapy had included needle aspiration biopsies followed by simple curettage and closure, the most common therapy for traumatic bone cysts. However, all treatment had proved unsuccessful for this patient. It was decided to treat the patient with a slightly unique method. After curettage of the lesion, the traumatic bone cyst was packed with a mixture of autogenous blood, harvested autogenous bone chips, and hydroxyapatite.

Glycogen storage disease and von Willebrand's disease implications for dental treatment: dental management of a pediatric patient.

Glycogen storage diseases (GSD) are metabolic disorders which impair the body's ability to store glucose and utilize it later, requiring patients to take multiple daily dietary supplementation with a high carbohydrate content. Patients undergoing this treatment modality are placed at increased risk for gross dental caries and other oral abnormalities. Additionally, GSD may prolong the patient's bleeding time, which may necessitate consultation with the treating physician. In the following case, our patient required a multidisciplinary approach to address not only her dental needs, but also to coordinate the management of both her GSD and an additional complication, von Willebrand's disease. This was best achieved in a hospital setting.