DNA damage in an estuarine fish inhabiting the vicinity of a major Brazilian port.

The Itaqui Port Complex (northeastern Brazil) is one of the largest Brazilian port facilities, whose effluents and waste are dumped directly into the estuarine waters. Although environmental monitoring has been a concern around this site, there has been no toxicogenetics study on organisms living in this environment. Thus, we assessed the toxicogenetics potential of the estuarine waters surrounding Itaqui, using the native catfish Sciades herzbergii as a biomonitor. We found a significantly higher frequency of genetic damage and mutations in the animals collected near to Itaqui in both seasons compared to the reference site (distant from Itaqui with no port activities). We also quantified chemical elements in the surface water and sediments near the port and found that clorine, phosphorus, zinc, and boron were above the limits set by the Brazilian legislation. We suggest that such contaminants are involved in the origin of DNA damage. Moreover, we recommend including toxicogenetics assays in the environmental monitoring of pollutants, as well as in the definition of their allowable limits, as they could be used as law enforcement tools and help to predict large-scale contamination events associated with port activities.

Patterns of copy number alterations in primary breast tumors of South African patients and their impact on functional cellular pathways.

Breast cancer is the most common and the leading cause of female mortality among South African (SA) women. Several non­biological and biological risk factors may be attributed to their observed high mortality rate; however, the molecular profiles associated with their breast tumors are poorly characterized. The present study examined the patterns of genome-wide copy number alterations (CNAs) and their potential impact on functional cellular pathways targeted by cancer driver genes in patients with breast cancer from the Western Cape region of SA. Array-comparative genomic hybridization analysis, performed in 28 cases of invasive breast cancer, revealed a mean number of 8.68±6.18 CNAs per case, affecting primarily the Xp22.3 and 6p21-p25 cytobands (57.14% of the cases), followed by 19p13.3-p13.11 (35.7%), 2p25.3-p24.3, 4p16.3-p15.3, 8q11.1-q24.3 and 16 p13.3-p11.2 (32.14%). Functional enrichment analysis of genes and microRNA targets mapped in these affected cytobands revealed critical cancer-associated pathways, including fatty acid biosynthesis and metabolism, extracellular matrix-receptor interaction, hippo and tumor protein p53 signaling pathways, which are regulated by known cancer genes, including CCND1, CDKN1A, MAPK1, MDM2, TP53 and SMAD2. An inverse correlation was observed among the number of CNAs and tumor size and grade; CNAs on the 4p and 6p cytobands were also inversely correlated with tumor grade. No association was observed in the number of CNAs and/or the affected cytobands and the different ethnic groups of the SA patients, indicating that their tumor genome is affected by CNAs, irrespectively of their genetic descent. Additional genomic tumor profiling in SA and other Sub-Saharan African patients with breast cancer is required to determine the associations of the CNAs observed with prognosis and clinical outcome.

Copy Number Analysis of the DLX4 and ERBB2 Genes in South African Breast Cancer Patients.

Breast cancer is one of the main causes of cancer death among South African women. Although several risk factors can be attributed to the observed high mortality rate, the biology of the tumors is not extensively investigated. Copy number gain of the DLX4 homeobox gene has been observed in breast cancer in association with poor prognosis and specific racial groups. Therefore, we aimed to assess the copy number and prognostic role of DLX4 in breast cancer from South African patients. Due to the co-location of ERBB2 and DLX4 in the 17q21 region, its copy number was also evaluated. Our results in the analysis of 66 cases demonstrated copy number gains of DLX4 and ERBB2 in 24.1 and 29.7% of the cases, respectively. Linear regression analysis showed no dependency between the copy number alterations in these genes. Although not significant, patients with DLX4 and ERBB2 gains presented a higher frequency of advanced-grade tumors. In addition, copy number alterations of these genes were not significantly differently observed in the 3 main racial groups of the Western Cape population: Colored, White, and Black. These findings indicate that gains of DLX4 and ERBB2 occur in South African breast cancer patients irrespectively of their race and factors known to influence prognosis.

Increased copy number of the DLX4 homeobox gene in breast axillary lymph node metastasis.

DLX4 is a homeobox gene strongly implicated in breast tumor progression and invasion. Our main objective was to determine the DLX4 copy number status in sentinel lymph node (SLN) metastasis to assess its involvement in the initial stages of the axillary metastatic process. A total of 37 paired samples of SLN metastasis and primary breast tumors (PBT) were evaluated by fluorescence in situ hybridization, quantitative polymerase chain reaction and array comparative genomic hybridization assays. DLX4 increased copy number was observed in 21.6% of the PBT and 24.3% of the SLN metastasis; regression analysis demonstrated that the DLX4 alterations observed in the SLN metastasis were dependent on the ones in the PBT, indicating that they occur in the primary tumor cell populations and are maintained in the early axillary metastatic site. In addition, regression analysis demonstrated that DLX4 alterations (and other DLX and HOXB family members) occurred independently of the ones in the HER2/NEU gene, the main amplification driver on the 17q region. Additional studies evaluating DLX4 copy number in non-SLN axillary lymph nodes and/or distant breast cancer metastasis are necessary to determine if these alterations are carried on and maintained during more advanced stages of tumor progression and if could be used as a predictive marker for axillary involvement.

Variabilidade genética de Bemisia tabaci (Gennadius) biótipo B (Hemiptera: Aleyrodidae) em cultivos olerícolas em São Luís, MA / Genetic variability of the Bemisia tabaci (Gennadius) biotype B (Hemiptera: Aleyrodidae) in vegetable crops in São Luís, State of Maranhão, Brazil

The RAPD technique is widely used to investigate the distinct genetic characteristics of the complex Bemisia tabaci (Gennadius), which is currently constituted of approximately 41 biotypes. The objective of this research was to characterize populations of whitefly collected in crops of agricultural producing areas in São Luís, MA, like okra, beans and pepper, using RAPD molecular markers. Females from nine whitefly populations were analyzed and compared with B. tabaci biotype B taken from poinsettia culture of Embrapa Genetic Resources and Biotechnology (Brasília, DF). Twelve out of the 20 primers tested produced specific band patterns suitable to confirm that the evaluated specimens belong to the biotype B of B. tabaci, despite the high percentage of detected polymorphism. The analysis of the 96 RAPD molecular markers generated indicated that the populations on okra, beans and pepper were grouped according to the host cultures, sharing 80, 76 and 45 percent of genetic similarity, respectively, when compared with the control population of B. tabaci biotype B. A lower selective pressure was observed with the population of whitefly collected on pepper and minor genetic variability in the whitefly populations collected on okra and bean, when compared with the control population.

A técnica de RAPD é amplamente empregada para investigar características genéticas distintas dentro do complexo Bemisia tabaci Gennadius, atualmente constituído de aproximadamente 41 biótipos. O objetivo desta pesquisa foi caracterizar populações de mosca-branca coletadas em culturas agrícolas do município de São Luís, MA, como quiabo, feijão e pimentão, utilizando marcadores moleculares RAPD. Fêmeas de nove populações de mosca-branca foram analisadas e comparadas com o biótipo B de B. tabaci proveniente de cultura de poinsétia da Embrapa Recursos Genéticos e Biotecnologia (Brasília, DF). Dos 20 iniciadores utilizados, 12 produziram padrões de bandas específicas, que permitiram confirmar que os espécimes avaliados pertencem ao grupo do biótipo B de B. tabaci, apesar da alta percentagem de polimorfismo detectado. Com os 96 marcadores moleculares RAPD gerados foi construído um dendrograma, que mostrou que as populações de quiabo, feijão e pimentão foram agrupadas de acordo com as culturas hospedeiras. A matriz de similaridade genética entre as populações de B. tabaci mostrou 80, 76 e 45 por cento similaridade genética entre as populações das culturas de quiabo, feijão e pimentão, respectivamente, quando comparadas com a população controle de B. tabaci biótipo B. Foi também observada menor pressão de seleção na população de mosca-branca coletada em pimentão e menor variabilidade genética nas populações de mosca-branca coletadas em quiabo e feijão, quando comparadas com a população controle.

[Genetic variability of the Bemisia tabaci (Gennadius) biotype B (Hemiptera: Aleyrodidae) in vegetable crops in São Luís, state of Maranhão, Brazil]. / Variabilidade genética de Bemisia tabaci (Gennadius) biótipo B (Hemiptera: Aleyrodidae) em cultivos olerícolas em São Luís, MA.

The RAPD technique is widely used to investigate the distinct genetic characteristics of the complex Bemisia tabaci (Gennadius), which is currently constituted of approximately 41 biotypes. The objective of this research was to characterize populations of whitefly collected in crops of agricultural producing areas in São Luís, MA, like okra, beans and pepper, using RAPD molecular markers. Females from nine whitefly populations were analyzed and compared with B. tabaci biotype B taken from poinsettia culture of Embrapa Genetic Resources and Biotechnology (Brasília, DF). Twelve out of the 20 primers tested produced specific band patterns suitable to confirm that the evaluated specimens belong to the biotype B of B. tabaci, despite the high percentage of detected polymorphism. The analysis of the 96 RAPD molecular markers generated indicated that the populations on okra, beans and pepper were grouped according to the host cultures, sharing 80, 76 and 45% of genetic similarity, respectively, when compared with the control population of B. tabaci biotype B. A lower selective pressure was observed with the population of whitefly collected on pepper and minor genetic variability in the whitefly populations collected on okra and bean, when compared with the control population.