Absence of mutations of the BRAF gene in malignant melanoma of soft parts (clear cell sarcoma of tendons and aponeuroses)

Malignant melanoma of soft parts (MMSP), also called clear cell sarcoma of tendons and aponeuroses, is cytogenetically characterized by the t(12;22)(q13;q12) resulting in the chimeric EWSR1/ATF1 gene. MMSP shares a number of morphologic, histologic, and immunohistochemical features with malignant melanoma of the skin, causing diagnostic difficulties in the distinction between MMSP and metastatic malignant melanoma with an unknown primary site. Recently, a high incidence of activating mutations in the kinase domain of the BRAF gene has been reported in malignant melanoma of the skin. The most common mutation (V599E) is the T1796A substitution in exon 15, leading to an exchange of valine for glutamic acid at position 599. Because of the extensive clinical, histologic, and immunohistochemic similarities with melanoma, we decided to analyze whether MMSP also has mutations in the BRAF gene. Eight MMSP with an EWSR1/ATF1 chimeric transcript, one soft tissue metastasis of a malignant melanoma of the skin, and one malignant melanoma cell line were examined. Both conventional melanomas had the exon 15 T1796A (V599E) mutation, but none of the MMSP was found to harbor any mutation in exon 11 or 15 of the BRAF gene. Our data further emphasize that MMSP and conventional malignant melanoma develop through different genetic pathways

Smartphone-Bases Reality Capture for Subsurface Utilities:Experiences from water utility companies in Denmark

Inaccurate and inconsistent documentation of subsurface utilities is a reoccurring problem in the construction industry affecting not only the end-users, but all actors involved in designing, constructing, and maintaining pipes, cables and other utilities hidden underground. In this study, a new method for 3D capturing of subsurface utilities, based on a newly developed Smartphone-based Reality Capture (RC) solution is explored. The research was divided into two parts. Firstly a testing of the method accuracy and secondly, an investigation of the usability of the method. The research results firstly showed that the RC solution is a feasible surveying method, that facilitate capturing of as-built utility assets, which can be used as a supporting tool to conventional surveying methods or alone, as the testing showed an accuracy of ±5 cm for the generated point clouds. Secondly the usability testing revealed that the RC solution benefited the utility owners by allowing time-savings on construction projects, as well as generating visual-realistic 3D models of exposed subsurface utilities to be used for quality assurance and planning of future utility work

Initial programme theory development:The first step in a realist evaluation of a cross-sectoral intervention for expectant Danish parents living with psychosocial risks

A distinct inequality in maternity care exists, and women with psychosocial risks are at a greater risk of adverse birth outcomes. In several high-income countries, a psychosocial risk assessment early in pregnancy is recommended so that expectant parents are offered an appropriate level of care which facilitates relevant, tailored interventions for those in need. In 2017, a cross-sectoral and interdisciplinary intervention for expectant parents with psychosocial risks was developed and implemented in the North Denmark Region. The development process of the intervention has not been reported and theory-based knowledge about how supportive interventions bring about change for expectant parents with psychosocial risks is scarce. Through the initial phase of a realist evaluation, we aimed to elicit key contexts and mechanisms of change regarding the intervention for expectant parents with psychosocial risks. Through an initial programme theory, this article illustrates how, for whom and in which contexts the intervention is intended to work. Data is comprised of intervention documents, 14 pilot observations and 29 realist interviews with key stakeholders. A thematic analytical approach inspired by retroductive thinking was applied to identify and analyse patterns related to the incentive of the intervention, its structure, intended outcomes, generative mechanisms and contextual matters. Generative mechanisms responsible for bringing about change in the intervention were identified as healthcare professionals' approach, continuity, trust, early intervention and social network. Cross-sectoral collaboration and healthcare professionals' competencies were assumed to be central stimulating contextual factors. The initial programme theory developed in this study will serve as the basis for further refinement via empirical testing in a later phase of the realist evaluation.</p

Expression levels of HMGA2 in adipocytic tumors correlate with morphologic and cytogenetic subgroups

Background: The HMGA2 gene encodes a protein that alters chromatin structure. Deregulation, typically through chromosomal rearrangements, of HMGA2 has an important role in the development of several mesenchymal neoplasms. These rearrangements result in the expression of a truncated protein lacking the acidic C-terminus, a fusion protein consisting of the AT-hook domains encoded by exons 1-3 and parts from another gene, or a full-length protein; loss of binding sites for regulatory microRNA molecules from the 3' untranslated region (UTR) of HMGA2 has been suggested to be a common denominator.Methods: Seventy adipocytic tumors, representing different morphologic and cytogenetic subgroups, were analyzed by qRT-PCR to study the expression status of HMGA2; 18 of these tumors were further examined by PCR to search for mutations or deletions in the 3'UTR.Results: Type (full-length or truncated) and level of expression varied with morphology and karyotype, with the highest levels in atypical lipomatous tumors and lipomas with rearrangements of 12q13-15 and the lowest in lipomas with 6p- or 13q-rearrangements, hibernomas, spindle cell lipomas and myxoid liposarcomas. All 18 examined tumors showed reduced or absent expression of the entire, or parts of, the 3'UTR, which was not due to mutations at the DNA level.Conclusion: In adipocytic tumors with deregulated HMGA2 expression, the 3'UTR is consistently lost, either due to physical disruption of HMGA2 or a shift to production of shorter 3'UTR

Centrosomal abnormalities, multipolar mitoses, and chromosomal instability in head and neck tumours with dysfunctional telomeres

Carcinomas of the head and neck typically exhibit complex chromosome aberrations but the underlying mutational mechanisms remain obscure. Evaluation of cell division dynamics in low-passage cell lines from three benign and five malignant head and neck tumours revealed a strong positive correlation between multipolarity of the mitotic spindle and the formation of bridges at anaphase in both benign and malignant tumours. Cells exhibiting a high rate of mitotic abnormalities also showed several chromosome termini lacking TTAGGG repeats and a high frequency of dicentric chromosomes. Multicolour karyotyping demonstrated a preferential involvement in structural rearrangements of chromosomes with deficient telomeres. The majority of malignant, mitotically unstable tumours expressed the reverse transcriptase subunit of telomerase. These data indicate that some of the genomic instability in head and neck tumours is initiated by telomere dysfunction, leading to the formation of dicentric chromosomes. These form chromosome bridges at mitosis that could prevent the normal anaphase-telophase transition. In turn, this may cause an accumulation of centrosomes and mitotic multipolarity. Telomerase expression does not confer total stability to the tumour genome but could be crucial for moderating the rate of chromosomal evolution

GLI1 (glioma-associated oncogene homolog 1)

Review on GLI1 (glioma-associated oncogene homolog 1), with data on DNA, on the protein encoded, and where the gene is implicated

Soft tissue tumors: Low grade fibromyxoid sarcoma

Review on Soft tissue tumors: Low grade fibromyxoid sarcoma, with data on clinics, and the genes involved