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A genetic predisposition for paragangliomas and adrenal or extra‐adrenal phaeochromocytomas was recognized years ago. Beside the well‐known syndromes associated with an increased risk of adrenal ...phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel ‘paraganglioma–phaeochromocytoma syndrome’ caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest‐derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent‐of‐origin effect for SDHD mutations. Life‐time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation.
Highlights • Melanoma and mesothelioma show a statistically significant co-occurrence in the general population. • Inherited melanoma and mesothelioma predisposition is shown by individual with ...germline mutations in BAP1. • This paper reports a patient with mesothelioma who carried a germline mutation in CDKN2A , a gene involved in familial melanoma. Thus, CDKN2A may also predispose to both these tumors. • This paper also suggests that other genes could be involved in this predisposition, because families with cases of both melanoma and mesothelioma and no mutations in either BAP1 or CDKN2A are presented. • Since BAP1 and CDKN2A are somatically mutated in both cancers, our results suggest that these tumors may share common stepwise carcinogenic pathways.
Lycosa erythrognatha Lucas, 1833 (Araneae: Lycosidae) is a predatory arthropod with potential for conservation biological control. In addition to being considered a bioindicator of environmental ...quality, this arthropod provides an important service for agriculture by reducing insect-pest populations. In this work we seek to understand how the plants Andropogon bicornis L., Saccharum angustifolium Nees and Eustachys retusa Lag (Poales: Poaceae) and their different clump sizes affect the population density, spatial distribution and determination of the minimum number of samples to estimate its population density during the winter. Among the evaluated host plants, S. angustifolium and A. bicornis presented higher population density than E. retusa, but we observed that the clump diameter significantly influences the population density and the minimum number of samples. We observed a gregarious behavior in plants of A. bicornis and E. retusa. For S. angustifolium, a uniform distribution was observed.
Abstract Cerambycidae beetles limit production and establishment of forest and fruit trees. Oncideres cervina Thomson, 1868 (Coleoptera: Cerambycidae) is one of the most important species. The ...objective was to record O. cervina girdling branches of Persea americana Mill. (Lauraceae) for the first time, check the number of oviposition incisions (Noi) as a function of the diameter of branch sections, period of emergence, and describe the larval-pupal chamber. Individuals of O. cervina were observed, for the first time, in P. americana orchards in Santa Maria, Rio Grande do Sul, Brazil. The middle section of branches (40-60 cm interval) had higher number of incisions. Girdled branches with a diameter of 40-50 mm had higher number of them. Adults emerged from November through January. Larval-pupal boreholes had diameters between 9 and 11 mm, and average tunnel length was 28 mm, with a mean volume of consumed wood of 4.3 mL. This information is useful for establishing integrated pest management practices against O. cervina in P. americana since this crop has a high added value and can be significantly compromised by attack by Cerambycidae beetles.
Resumo Os besouros da família Cerambycidae limitam a produção e o estabelecimento de essências florestais e frutíferas. Oncideres cervina Thomson, 1868 (Coleoptera: Cerambycidae) é uma das espécies mais importantes. O objetivo foi registrar O. cervina danificando ramos de Persea americana Mill. (Lauraceae) pela primeira vez, verificar o número de incisões de postura em relação ao diâmetro das secções dos ramos, período de emergência e descrever a galeria larval-pupal. Indivíduos de O. cervina foram observados pela primeira vez em pomares de P. americana em Santa Maria, Rio Grande do Sul, Brasil. A secção média dos ramos (intervalo de 40-60 cm) apresentou maior número de incisões. Ramos danificados com diâmetro de 40-50 mm tiveram maior número delas. Adultos emergiram de novembro a janeiro. Os orifícios larvais-pupais tinham diâmetros entre 9 e 11 mm, e o comprimento médio da galeria era de 28 mm, com um volume médio de madeira consumida de 4,3 mL. Essas informações são úteis para estabelecer práticas integradas de manejo de pragas contra O. cervina em P. americana, já que essa cultura tem alto valor agregado e pode ser significativamente comprometida pelo ataque de besouros da família Cerambycidae.
•The Lynch syndrome (LS) is an autosomal dominant condition usually characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes.•We report about a 47 years-old female affected by ...endometrial cancer (EC) with an extremely rare germline heterozygous variant in the MSH2 gene (c.562G > T p. (Glu188Ter), exon 3) that is likely pathogenic.
The Lynch syndrome (LS) is an autosomal dominant condition usually characterized by germline pathogenic variants in DNA mismatch repair (MMR) genes. Despite the guidelines now available, determining the pathogenicity of rare variants remains challenging, as the clinical significance of a genetic variant could be uncertain, but it may represent a disease-associated variation in the aforementioned genes. In this case report we will describe the case of a 47 years-old female affected by endometrial cancer (EC) with an extremely rare germline heterozygous variant in the MSH2 gene (c.562G > T p. (Glu188Ter), exon 3) that is likely pathogenic, and a family history consistent with LS.
Purpose
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary endocrine syndrome caused by pathogenic variants in
MEN1
tumor suppressor gene. Diagnosis is commonly based on clinical criteria and ...confirmed by genetic testing. The objective of the present study was to report on a MEN1 case characterized by multiple pancreatic glucagonomas, with particular concern on the possible predisposing genetic defects.
Methods
While conducting an extensive review of the most recent scientific evidence on the unusual glucagonoma familial forms, we analyzed the
MEN1
gene in a 35-year-old female with MEN1, as well as her son and daughter, using Sanger and next-generation sequencing (NGS) approaches. We additionally explored the functional and structural consequences of the identified variant using in silico analyses.
Results
NGS did not show any known pathogenic variant in the tested regions. However, a new non-conservative variant in exon 4 of
MEN1
gene was found in heterozygosity in the patient and in her daughter, resulting in an amino acid substitution from hydrophobic cysteine to hydrophilic arginine at c.703T > C, p.(Cys235Arg). This variant is absent from populations databases and was never reported in full papers: its characteristics, together with the high specificity of the patient’s clinical phenotype, pointed toward a possible causative role.
Conclusion
Our findings confirm the need for careful genetic analysis of patients with MEN1 and establish a likely pathogenic role for the new p.(Cys235Arg) variant, at least in the rare subset of MEN1 associated with glucagonomas.
Germline mutations in
BRCA1 and
BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on ...multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in
BRCA1 or
BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in
BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%–78%) for breast cancer and 39% (18%–54%) for ovarian cancer. The corresponding estimates for
BRCA2 were 45% (31%–56%) and 11% (2.4%–19%). Relative risks of breast cancer declined significantly with age for
BRCA1-mutation carriers (
P trend .0012) but not for
BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for
BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.
Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed ...at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status.
We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series.
Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. 9% vs 18%, p = 0.019 and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00–3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004–0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant.
In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.
•Hypersensitivity reactions (HSRs) to carboplatin are frequent in pretreated ovarian cancer (OC) patients (pts).•The role of BRCA mutations (mut) as a risk factor has been suggested.•We demonstrate that BRCAmut pts. have an increased risk of HSRs which is not justified by longer drug exposure only.•Receiving pegylated liposomal doxorubicin was a protective factor in our series.•The meta-analysis of literature, though results are heterogeneous, confirms the role of BRCAmut in increasing HSRs risk.
Background
Array‐comparative genomic hybridization (array‐CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID).
...Aims
Identification of genomic disorders in DD/ID.
Materials and methods
We performed a comprehensive array‐CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs.
Results
We identified non‐benign CNVs in 29% of patients. Amongst the pathogenic variants (11%), detected with a yield consistent with the literature, we found rare genomic disorders and CNVs spanning known disease genes. We further identified and discussed 51 cases with likely pathogenic CNVs spanning novel candidate genes, including genes encoding synaptic components and/or proteins involved in corticogenesis. Additionally, we identified two deletions spanning potential Topological Associated Domain (TAD) boundaries probably affecting the regulatory landscape.
Discussion and conclusion
We show how phenotypic and genetic analyses of array‐CGH data allow unraveling complex cases, identifying rare disease genes, and revealing unexpected position effects.
Certain characteristics of some vegetable crops allow multiple harvests during the production cycle; however, to our knowledge, no study has described the behavior of fruit production with ...progression of the production cycle in vegetable crops with multiple harvests that present data overdispersion. We aimed to characterize the data overdispersion of zero-inflated variables and identify the behavior of these variables during the production cycle of several vegetable crops with multiple harvests. Data from 11 uniformity trials were used without applying treatments; these comprise the database from the Experimental Plants Group at the Federal University of Santa Maria, Brazil. The trials were conducted using four horticultural species grown during different cultivation seasons, cultivation environments, and experimental structures. Although at each harvest, a larger number of basic units with harvest fruit was observed than units without harvest fruit, the basic unit percentage without fruit was high, generating an overdispersion within each individual harvest. The variability within each harvest was high and increased with the evolution of the production cycle of Capsicum annuum, Solanum lycopersicum var. cerasiforme, Phaseolus vulgaris, and Cucurbita pepo species. However, the correlation coefficient between the mean weight and number of harvest fruits tended to remain constant during the crop production cycle. These behaviors show that harvest management should be done individually, at each harvest, such that data overdispersion is reduced.
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