Very Rare Amelanotic Lentigo Maligna Melanoma with Skull Roof Invasion.
Ontology highlight
ABSTRACT:
SUBMITTER: Wollina U
PROVIDER: S-EPMC5535657 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundThe study of convergently acquired adaptations allows fundamental insight into life's evolutionary history. Within lepidosaur reptiles-i.e. lizards, tuatara, and snakes-a fully fossorial ('burrowing') lifestyle has independently evolved in most major clades. However, despite their consistent use of the skull as a digging tool, cranial modifications common to all these lineages are yet to be found. In particular, bone microanatomy, although highly diagnostic for lifestyle, remains unexplored in the lepidosaur cranium. This constitutes a key gap in our understanding of their complexly interwoven ecology, morphology, and evolution. In order to bridge this gap, we reconstructed the acquisition of a fossorial lifestyle in 2813 lepidosaurs and assessed the skull roof compactness from microCT cross-sections in a representative subset (n =?99). We tested this and five macroscopic morphological traits for their convergent evolution.ResultsWe found that fossoriality evolved independently in 54 lepidosaur lineages. Furthermore, a highly compact skull roof, small skull diameter, elongate cranium, and low length ratio of frontal and parietal were repeatedly acquired in concert with a fossorial lifestyle.ConclusionsWe report a novel case of convergence that concerns lepidosaur diversity as a whole. Our findings further indicate an early evolution of fossorial modifications in the amphisbaenian 'worm-lizards' and support a fossorial origin for snakes. Nonetheless, our results suggest distinct evolutionary pathways between fossorial lizards and snakes through different contingencies. We thus provide novel insights into the evolutionary mechanisms and constraints underlying amniote diversity and a powerful tool for the reconstruction of extinct reptile ecology.
| S-EPMC7702674 | biostudies-literature
Project description:Received wisdom in the field of fungal biology holds that the process of editing a genome by transformation and homologous recombination is inherently mutagenic. However, that belief is based only on circumstantial evidence. We provide the first direct measurement of the effects of transformation on the genome by sequencing the genomes of 29 transformants and 30 untransformed controls to high coverage. Contrary to the received wisdom, our results show that transformation of DNA flanked by long targeting sequences, followed by homologous recombination and selection on a drug marker, is extremely safe. Gene deletion may select for a few mutations that occur after transformation, but even then we found fewer than two point mutations per gene deletion strain. We also tested these strains for changes in gene expression and found only a few genes that were consistently differentially expressed between wild types and strains with a drug resistance marker inserted. As part of this process, we provide the first published genome sequence of the commonly used laboratory strain Cryptococcus neoformans var. grubii strain KN99.
2017-09-26 | GSE104198 | GEO
Project description:Bombay phenotype, H partially deficient non secretor phenotype and Para-Bombay phenotype are rare blood groups with deficiency or absence of H antigen. A 52-year-old female with Chronic suppurative otitis media was referred to our hospital. The primary serologic results of ABO blood typing were discrepant in forward and reverse grouping. Further, the saliva secretion tests, the pedigree studies and the sequence analysis were performed to confirm the rare phenotype. The patient was diagnosed as a variant H-deficient phenotype, secretor (para-bombay). Red cells of the patient have no H antigens, and it's a very interesting thing that there were two opposite results in the saliva test by using different anti-H. The test showed that H substances were present in the saliva by using anti-H from Libo Biotechnology Co, while which were absent by using anti-H from Shanghai blood center. The patient's Lewis phenotype was Le (a-b+). Anti-HI was present in the sera of her. The sequence of the ABO gene of the patient was 261delG and 467C>T heterozygote by direct DNA sequencing and was assigned as A102/O01. There were two mutations of the patient's FUT1, 328G/A and 658C/T, which were identified by DNA sequencing compared with the reference sequence (GenBank, NG_007510.2). In this case, we report a patient with particular H-deficient phenotype, secretor, which showed opposite results in the saliva test by using anti-H from different sources. We suspect that it is a variant of para-Bombay phenotype.
| S-EPMC6186255 | biostudies-literature
Project description:An ectopic supernumerary tooth causing the formation of rhinolith was never reported before in the medical literature. A 30 years old male patient presented to our hospital with one sided nasal obstruction, recurrent epistaxis, and nasal discharge. Anterior rhinoscopy, nasal endoscopy and X-ray paranasal sinuses revealed a rhinolith in the left nasal cavity. Preoperative evaluation and post operative examination of the specimen proved that the nidus of rhinolith was a supernumerary ectopic tooth.
| S-EPMC3851516 | biostudies-literature
Project description:In this article, we introduced a case of rare congenital anomalies that was asymptomatic until adulthood and was complicated by infective endocarditis and dissection of aortic valve leaflet.
| S-EPMC8212014 | biostudies-literature
Project description:Uterine leiomyosarcoma (uLMS) is a rare and aggressive malignancy with poor clinical outcomes. Even when localized, uLMS is associated with high rates of local and distant recurrences that are usually fatal. Common sites of recurrence are lung, liver, pelvic lymph nodes, and vertebral and long bones, though atypical patterns of recurrence have been described. Among them, intracranial recurrence appears as a rare finding, almost exceptional in skull and dura. We describe the case of a solitary skull metastasis from uLMS in a 39-year-old woman, which represents the third reported case of skull recurrence in literature. After multidisciplinary discussion, the patient underwent surgery and received adjuvant radiotherapy. After 4 months, she is currently alive, without evidence of extracranial disease. This case highlights the importance of suspecting and recognizing atypical and extremely rare metastasis to this region. We encourage the need for large case series in order to provide further information about cranial recurrences of uLMS taking into account the paucity of data currently available in literature and the frequently unpredictable behavior of this rare and highly lethal disease.
| S-EPMC7308452 | biostudies-literature
Project description:Known high-risk cutaneous malignant melanoma (CMM) genes account for melanoma risk in <40% of melanoma-prone families, suggesting the existence of additional high-risk genes or perhaps a polygenic mechanism involving multiple genetic modifiers. The goal of this study was to systematically characterize rare germline variants in 42 established melanoma genes among 144 CMM patients in 76 American CMM families without known mutations using data from whole-exome sequencing. We identified 68 rare (<0.1% in public and in-house control datasets) nonsynonymous variants in 25 genes. We technically validated all loss-of-function, inframe insertion/deletion, and missense variants predicted as deleterious, and followed them up in 1, 559 population-based CMM cases and 1, 633 controls. Several of these variants showed disease co-segregation within families. Of particular interest, a stopgain variant in TYR was present in five of six CMM cases/obligate gene carriers in one family and a single population-based CMM case. A start gain variant in the 5'UTR region of PLA2G6 and a missense variant in ATM were each seen in all three affected people in a single family, respectively. Results from rare variant burden tests showed that familial and population-based CMM patients tended to have higher frequencies of rare germline variants in albinism genes such as TYR, TYRP1, and OCA2 (P < 0.05). Our results suggest that rare nonsynonymous variants in low- or intermediate-risk CMM genes may influence familial CMM predisposition, warranting further investigation of both common and rare variants in genes affecting functionally important pathways (such as melanogenesis) in melanoma risk assessment.
| S-EPMC5886297 | biostudies-literature
Project description:Melanoma patients with oncogenic BRAF(V600E) mutation have poor prognoses. While the role of BRAF(V600E) in tumorigenesis is well established, its involvement in metastasis that is clinically observed in melanoma patients remains a topic of debate. Here, we show that BRAF(V600E) melanoma cells have extensive invasion activity as assayed by the generation of F-actin and cortactin foci that mediate membrane protrusion, and degradation of the extracellular matrix (ECM). Inhibition of BRAF(V600E) blocks melanoma cell invasion. In a BRAF(V600E)-driven murine melanoma model or in patients' tumor biopsies, cortactin foci decrease upon inhibitor treatment. In addition, genome-wide expression analysis shows that a number of invadopodia-related genes are downregulated after BRAF(V600E) inhibition. Mechanistically, BRAF(V600E) induces phosphorylation of cortactin and the exocyst subunit Exo70 through ERK, which regulates actin dynamics and matrix metalloprotease secretion, respectively. Our results provide support for the role of BRAF(V600E) in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma.
| S-EPMC4889462 | biostudies-literature
Project description:Melanoma cells use different migratory strategies to exit the primary tumor mass and invade surrounding and subsequently distant tissues. We reported previously that ADAR1 expression is downregulated in metastatic melanoma, thereby facilitating proliferation. Here we show that ADAR1 silencing enhances melanoma cell invasiveness and ITGB3 expression. The enhanced invasion is reversed when ITGB3 is blocked with antibodies. Re-expression of wild-type or catalytically inactive ADAR1 establishes this mechanism as independent of RNA editing. We demonstrate that ADAR1 controls ITGB3 expression both at the post-transcriptional and transcriptional levels, via miR-22 and PAX6 transcription factor, respectively. These are proven here as direct regulators of ITGB3 expression. miR-22 expression is controlled by ADAR1 via FOXD1 transcription factor. Clinical relevance is demonstrated in patient-paired progression tissue microarray using immunohistochemistry. The novel ADAR1-dependent and RNA-editing-independent regulation of invasion, mediated by ITGB3, strongly points to a central involvement of ADAR1 in cancer progression and metastasis.
| S-EPMC5981216 | biostudies-literature
Project description:BackgroundThe transforming growth factor-beta (TGF-beta) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-beta signaling.MethodsWe used real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting to determine GLI2 expression in human melanoma cell lines and subsequently classified them as GLI2high or as GLI2low according to their relative GLI2 mRNA and protein expression levels. GLI2 expression was reduced in a GLI2high cell line with lentiviral expression of short hairpin RNA targeting GLI2. We assessed the role of GLI2 in melanoma cell invasiveness in Matrigel assays. We measured secretion of matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography and expression of E-cadherin by western blotting and RT-PCR. The role of GLI2 in development of bone metastases was determined following intracardiac injection of melanoma cells in immunocompromised mice (n = 5-13). Human melanoma samples (n = 79) at various stages of disease progression were analyzed for GLI2 and E-cadherin expression by immunohistochemistry, in situ hybridization, or RT-PCR. All statistical tests were two-sided.ResultsAmong melanoma cell lines, increased GLI2 expression was associated with loss of E-cadherin expression and with increased capacity to invade Matrigel and to form bone metastases in mice (mean osteolytic tumor area: GLI2high vs GLI2low, 2.81 vs 0.93 mm(2), difference = 1.88 mm(2), 95% confidence interval [CI] = 1.16 to 2.60, P < .001). Reduction of GLI2 expression in melanoma cells that had expressed high levels of GLI2 substantially inhibited both basal and TGF-beta-induced cell migration, invasion (mean number of Matrigel invading cells: shGLI2 vs shCtrl (control), 52.6 vs 100, difference = 47.4, 95% CI = 37.0 to 57.8, P = .024; for shGLI2 + TGF-beta vs shCtrl + TGF-beta, 31.0 vs 161.9, difference = -130.9, 95% CI = -96.2 to -165.5, P = .002), and MMP secretion in vitro and the development of experimental bone metastases in mice. Within human melanoma lesions, GLI2 expression was heterogeneous, associated with tumor regions in which E-cadherin was lost and increased in the most aggressive tumors.ConclusionGLI2 was directly involved in driving melanoma invasion and metastasis in this preclinical study.
| S-EPMC2914763 | biostudies-literature